ORCID Profile
0000-0002-8231-282X
Current Organisation
IT University of Copenhagen
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Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8FO00387D
Abstract: A mechanistic insight into the immunomodulatory effects of a purified procyanidin fraction from cocoa beans.
Publisher: Elsevier BV
Date: 10-2013
Publisher: The American Association of Immunologists
Date: 06-2020
Abstract: Fermentable dietary fibers promote the growth of beneficial bacteria, can enhance mucosal barrier integrity, and reduce chronic inflammation. However, effects on intestinal type 2 immune function remain unclear. In this study, we used the murine whipworm Trichuris muris to investigate the effect of the fermentable fiber inulin on host responses to infection regimes that promote distinct Th1 and Th2 responses in C57BL/6 mice. In uninfected mice, dietary inulin stimulated the growth of beneficial bacteria, such as Bifidobacterium (Actinobacteria) and Akkermansia (Verrucomicrobia). Despite this, inulin prevented worm expulsion in normally resistant mice, instead resulting in chronic infection, whereas mice fed an equivalent amount of nonfermentable fiber (cellulose) expelled worms normally. Lack of expulsion in the mice fed inulin was accompanied by a significantly Th1-skewed immune profile characterized by increased T-bet+ T cells and IFN-γ production in mesenteric lymph nodes, increased expression of Ido1 in the cecum, and a complete absence of mast cell and IgE production. Furthermore, the combination of dietary inulin and high-dose T. muris infection caused marked dysbiosis, with expansion of the Firmicutes and Proteobacteria phyla, near elimination of Bacteroidetes, and marked reductions in cecal short-chain fatty acids. Neutralization of IFN-γ during infection abrogated Ido1 expression and was sufficient to restore IgE production and worm expulsion in inulin-fed mice. Our results indicate that, whereas inulin promoted gut health in otherwise healthy mice, during T. muris infection, it exacerbated inflammatory responses and dysbiosis. Thus, the positive effects of fermentable fiber on gut inflammation appear to be context dependent, revealing a novel interaction between diet and infection.
Publisher: Oxford University Press (OUP)
Date: 09-11-2017
Abstract: Ascaris suum is a helminth parasite of pigs closely related to its human counterpart, A. lumbricoides, which infects almost 1 billion people. Ascaris is thought to modulate host immune and inflammatory responses, which may drive immune hyporesponsiveness during chronic infections. Using transcriptomic analysis, we show here that pigs with a chronic A. suum infection have a substantial suppression of inflammatory pathways in the intestinal mucosa, with a broad downregulation of genes encoding cytokines and antigen-processing and costimulatory molecules. A. suum body fluid (ABF) suppressed similar transcriptional pathways in human dendritic cells (DCs) in vitro. DCs exposed to ABF secreted minimal amounts of cytokines and had impaired production of cyclooxygengase-2, altered glucose metabolism, and reduced capacity to induce interferon-gamma production in T cells. Our in vivo and in vitro data provide an insight into mucosal immune modulation during Ascaris infection, and show that A. suum profoundly suppresses immune and inflammatory pathways.
Publisher: Public Library of Science (PLoS)
Date: 08-05-2014
Publisher: Cold Spring Harbor Laboratory
Date: 18-07-2022
DOI: 10.1101/2022.07.15.500167
Abstract: The influence of diet on immune function and resistance to enteric infection and disease is becoming ever more established. Highly processed, refined diets can lead to inflammation and gut microbiome dysbiosis, whilst health-promoting dietary components such as phytonutrients and fermentable fibres are thought to promote a healthy microbiome and balanced mucosal immunity. Chicory ( Cichorium intybus ) is a leafy green vegetable rich in fibres and bioactive compounds that may promote gut health. Unexpectedly, we here show that incorporation of chicory into semisynthetic AIN93G diets renders mice susceptible to infection with enteric helminths. Mice fed a high level of chicory leaves (10% dry matter) had a more erse gut microbiota, but a diminished type-2 immune response to infection with the intestinal roundworm Heligmosomoides polygyrus . Furthermore, the chicory-supplemented diet significantly increased burdens of the caecum-dwelling whipworm Trichuris muris , concomitant with a highly skewed type-1 immune environment in caecal tissue. The chicory-supplemented diet was rich in non-starch polysaccharides, particularly uronic acids (the monomeric constituents of pectin). In accordance, mice fed pectin-supplemented AIN93G diets had higher T. muris burdens and reduced IgE production and expression of genes involved in type-2 immunity. Importantly, treatment of pectin-fed mice with exogenous IL-25 restored type-2 responses and was sufficient to allow T. muris expulsion. Collectively, our data suggest that increasing levels of fermentable, non-starch polysaccharides in refined diets compromises immunity to helminth infection in mice. This diet-infection interaction may inform new strategies for manipulating the gut environment to promote resistance to enteric parasites.
Publisher: Springer Science and Business Media LLC
Date: 20-12-2011
DOI: 10.1038/NCOMMS1615
Publisher: Springer Science and Business Media LLC
Date: 14-06-2023
DOI: 10.1186/S12915-023-01640-Z
Abstract: The influence of diet on immune function and resistance to enteric infection and disease is becoming ever more established. Highly processed, refined diets can lead to inflammation and gut microbiome dysbiosis, whilst health-promoting dietary components such as phytonutrients and fermentable fibres are thought to promote a healthy microbiome and balanced mucosal immunity. Chicory ( Cichorium intybus ) is a leafy green vegetable rich in fibres and bioactive compounds that may promote gut health. Unexpectedly, we here show that incorporation of chicory into semisynthetic AIN93G diets renders mice susceptible to infection with enteric helminths. Mice fed a high level of chicory leaves (10% dry matter) had a more erse gut microbiota, but a diminished type-2 immune response to infection with the intestinal roundworm Heligmosomoides polygyrus . Furthermore, the chicory-supplemented diet significantly increased burdens of the caecum-dwelling whipworm Trichuris muris , concomitant with a highly skewed type-1 immune environment in caecal tissue. The chicory-supplemented diet was rich in non-starch polysaccharides, particularly uronic acids (the monomeric constituents of pectin). In accordance, mice fed pectin-supplemented AIN93G diets had higher T. muris burdens and reduced IgE production and expression of genes involved in type-2 immunity. Importantly, treatment of pectin-fed mice with exogenous IL-25 restored type-2 responses and was sufficient to allow T. muris expulsion. Collectively, our data suggest that increasing levels of fermentable, non-starch polysaccharides in refined diets compromises immunity to helminth infection in mice. This diet-infection interaction may inform new strategies for manipulating the gut environment to promote resistance to enteric parasites.
Publisher: Springer Science and Business Media LLC
Date: 21-07-2021
DOI: 10.1038/S42003-021-02408-3
Abstract: Proanthocyanidins (PAC) are dietary compounds that have been extensively studied for beneficial health effects due to their anti-inflammatory properties. However, the structure-function relationships of PAC and their mode-of-action remain obscure. Here, we isolated a wide range of erse PAC polymer mixtures of high purity from plant material. Polymer size was a key factor in determining the ability of PAC to regulate inflammatory cytokine responses in murine macrophages. PAC polymers with a medium (9.1) mean degree of polymerization (mDP) induced substantial transcriptomic changes, whereas PAC with either low (2.6) or high (12.3) mDP were significantly less active. Short-term oral treatment of mice with PAC modulated gene pathways connected to nutrient metabolism and inflammation in ileal tissue in a polymerization-dependent manner. Mechanistically, the bioactive PAC polymers modulated autophagic flux and inhibited lipopolysaccharide-induced autophagy in macrophages. Collectively, our results highlight the importance of defined structural features in the health-promoting effects of PAC-rich foods.
Publisher: Frontiers Media SA
Date: 09-11-2018
Publisher: Cambridge University Press (CUP)
Date: 03-03-2016
DOI: 10.1017/S0031182016000287
Abstract: Chicory is a perennial crop that has been investigated as a forage source for outdoor-reared ruminants and pigs, and has been reported to have anthelmintic properties. Here, we investigated in vitro anthelmintic effects of forage chicory-extracts against the highly prevalent swine parasites Ascaris suum and Oesophagostomum dentatum. Methanol extracts were prepared and purified from two different cultivars of chicory (Spadona and Puna II). Marked differences were observed between the anthelmintic activity of extracts from the two cultivars. Spadona extracts had potent activity against A. suum third (L3) and fourth (L4) – stage larvae, as well as O. dentatum L4 and adults, whereas Puna II extracts had less activity against A. suum and no activity towards O. dentatum L4. Transmission-electron microscopy of A. suum L4 exposed to Spadona extracts revealed only subtle changes, perhaps indicative of a specific anthelmintic effect rather than generalized toxicity. Ultra-high liquid chromatography-mass spectrometry analysis revealed that the purified extracts were rich in sesquiterpene lactones (SL), and that the SL profile differed significantly between cultivars. This is the first report of anthelmintic activity of forage chicory towards swine nematodes. Our results indicate a significant anthelmintic effect, which may possibly be related to SL composition.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.PARINT.2016.04.001
Abstract: Proanthocyanidins (PAC) are a class of plant secondary metabolites commonly found in the diet that have shown potential to control gastrointestinal nematode infections. The anti-parasitic mechanism(s) of PAC remain obscure, however the protein-binding properties of PAC suggest that disturbance of key enzyme functions may be a potential mode of action. Glutathione-S-transferases (GSTs) are essential for parasite detoxification and have been investigated as drug and vaccine targets. Here, we show that purified PAC strongly inhibit the activity of both recombinant and native GSTs from the parasitic nematode Ascaris suum. As GSTs are involved in detoxifying xenobiotic substances within the parasite, we hypothesised that this inhibition may render parasites hyper-susceptible to anthelmintic drugs. Migration inhibition assays with A. suum larvae demonstrated that the potency of levamisole (LEV) and ivermectin (IVM) were significantly increased in the presence of PAC purified from pine bark (4.6-fold and 3.2-fold reduction in IC50 value for LEV and IVM, respectively). Synergy analysis revealed that the relationship between PAC and LEV appeared to be synergistic in nature, suggesting a specific enhancement of LEV activity, whilst the relationship between PAC and IVM was additive rather than synergistic, suggesting independent actions. Our results demonstrate that these common dietary compounds may increase the efficacy of synthetic anthelmintic drugs in vitro, and also suggest one possible mechanism for their well-known anti-parasitic activity.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.PHYTOCHEM.2015.12.005
Abstract: Proanthocyanidins (PA) from shea (Vitellaria paradoxa) meal were investigated by thiolytic degradation with benzyl mercaptan and the reaction products were analysed by high performance liquid chromatography-mass spectrometry. These PA were galloylated (≈40%), contained only B-type linkages and had a high proportion of prodelphinidins (>70%). The mean degree of polymerisation was 8 (i.e. average molecular size was 2384Da) and epigallocatechin gallate (EGCg) was the major flavan-3-ol subunit in PA. Shea meal also proved to be a potentially valuable source for extracting free flavan-3-ol-O-gallates, especially EGCg (575mg/kg meal), which is known for its health and anti-parasitic benefits. Proanthocyanidins were isolated and tested for bioactivity against Ascaris suum, which is an important parasite of pigs. Migration and motility tests revealed that these PA have potent activity against this parasitic nematode.
Publisher: Cold Spring Harbor Laboratory
Date: 12-10-2021
DOI: 10.1101/2021.10.12.464117
Abstract: Bioactive dietary components may considerably influence intestinal health and resistance to enteric disease. Proanthocyanidins (PAC) are dietary polyphenols with putative health-promoting activity that have been increasingly studied for their anti-inflammatory and immunomodulatory effects. However, whether dietary PAC can regulate type-2 immune function and inflammation at mucosal surfaces remains unclear. Here, we investigated whether diets supplemented with purified PAC modulated pulmonary and intestinal mucosal immune responses during infection with the helminth parasite Ascaris suum in pigs. A. suum infection induced a type 2-biased immune response in lung and intestinal tissues, characterized by pulmonary granulocytosis, increased Th2/Th1 T cell ratios in tracheal-bronchial lymph nodes, intestinal eosinophilia, and modulation of genes involved in mucosal barrier function and immunity. We observed that PAC had only minor effects on pulmonary immune responses, regardless of concurrent A. suum infection. However, RNA-sequencing of intestinal tissues revealed that dietary PAC significantly enhanced transcriptional responses related to immune function, antioxidant responses, and cellular stress activity, both in uninfected and A. suum -infected animals. A. suum infection and dietary PAC both induced distinct changes in gut microbiota composition, primarily in the jejunum and colon, respectively. Notably, PAC substantially increased Limosilactobacillus reuteri abundance in the colon of both naïve and A. suum -infected animals. Thus, dietary PAC may have distinct beneficial effects on intestinal health during infection with mucosal pathogens, whilst having limited activity to modulate naturally-induced type-2 pulmonary inflammation. Our results shed further light on the mechanisms underlying the health-promoting properties of PAC-rich foods, and may aid in the design of novel dietary supplements to regulate mucosal inflammatory responses in the gastrointestinal tract.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.VETIMM.2017.06.004
Abstract: Dietary phytonutrients such as cinnamaldehyde (CA) may contribute to immune function during pathogen infections, and CA has been reported to have positive effects on gut health when used as feed additive for livestock. Here, we investigated whether CA could enhance antibody production and specific immune responses during infection with an enteric pathogen. We examined the effect of dietary CA on plasma antibody levels in parasite-naïve pigs, and subsequently acquisition of humoral immune responses during infection with the parasitic nematode Ascaris suum. Parasite-naïve pigs fed diets supplemented with CA had higher levels of total IgA and IgG in plasma, and A. suum-infected pigs fed CA had higher levels of parasite-specific IgM and IgA in plasma 14days post-infection. Moreover, dietary CA increased expression of genes encoding the B-cell marker CD19, sodium/glucose co-transporter1 (SCA5L1) and glucose transporter 2 (SLC2A2) in the jejunal mucosa of A.suum-infected pigs. Dietary CA induced only limited changes in the composition of the prokaryotic gut microbiota of A. suum-infected pigs, and in vitro experiments showed that CA did not directly induce proliferation or increase secretion of IgG and IgA from lymphocytes. Our results demonstrate that dietary CA can significantly enhance acquisition of specific immune responses in pigs. The underlying mechanism remains obscure, but apparently does not derive simply from direct contact between CA and host lymphocytes and appears to be independent of the gut microbiota.
Publisher: MDPI AG
Date: 24-05-2023
DOI: 10.3390/PATHOGENS12060755
Abstract: ABC transporters, a family of ATP-dependent transmembrane proteins, are responsible for the active transport of a wide range of molecules across cell membranes, including drugs, toxins, and nutrients. Nematodes possess a great ersity of ABC transporters however, only P-glycoproteins have been well-characterized compared to other classes. The ABC transport proteins have been implicated in developing resistance to various classes of anthelmintic drugs in parasitic nematodes their role in plant and human parasitic nematodes still needs further investigation. Therefore, ABC transport proteins offer a potential opportunity to develop nematode control strategies. Multidrug resistance inhibitors are becoming more attractive for controlling nematodes due to their potential to increase drug efficacy in two ways: (i) by limiting drug efflux from nematodes, thereby increasing the amount of drug that reaches its target site, and (ii) by reducing drug excretion by host animals, thereby enhancing drug bioavailability. This article reviews the role of ABC transporters in the survival of parasitic nematodes, including the genes involved, their regulation and physiological roles, as well as recent developments in their characterization. It also discusses the association of ABC transporters with anthelmintic resistance and the possibility of targeting them with next-generation inhibitors or nutraceuticals (e.g., polyphenols) to control parasitic infections.
Publisher: CSIRO Publishing
Date: 2008
DOI: 10.1071/EA08064
Abstract: Immune-mediated scouring in sheep is a mucosal hypersensitivity response incited by infective larvae of gastrointestinal nematodes in the southern half of Australia and in New Zealand, regions characterised by a Mediterranean, winter-rainfall climate. To gain insights into the underlying mechanism(s), this study investigated the relationship between nematode infection of sheep in pens, faecal dry matter and release of inflammatory mediators in the intestinal tract. Six worm-free, immune rams received a dose of 3000 Trichostrongylus third stage larvae (L3) and 3000 Ostertagia L3 per week for 6 weeks, after which they were euthanased. Three rams acted as uninfected controls. Faecal dry matter was significantly lower in the infected group from the first week of infection until the end of the trial. Concentrations of cysteinyl leukotrienes and prostaglandin E2 were higher in mucus from both the abomasum and the small intestine of infected rams compared with controls. Within the infected group, concentrations of both mediators were higher in mucus from the small intestine than from the abomasum. There were greater numbers of eosinophilic granulocytes and mucosal mast cells in abomasal and small-intestinal tissue sections from infected rams compared with the controls. The results are consistent with the hypothesis that nematode infection causes an inflammatory response in the gastrointestinal mucosa, characterised by increased fluid secretion.
Publisher: Cambridge University Press (CUP)
Date: 27-10-2020
DOI: 10.1017/S0007114520004225
Abstract: Hyperprolific sows rear more piglets than they have teats, and to accommodate this, milk replacers are often offered as a supplement. Milk replacers are based on bovine milk, yet components of vegetable origin are often added. This may reduce growth, but could also accelerate maturational changes. Therefore, we investigated the effect of feeding piglets a milk replacer with gradually increasing levels of wheat flour on growth, gut enzyme activity and immune function compared with a diet based entirely on bovine milk. The hypothesis tested was that adding a starch component (wheat flour) induces maturation of the mucosa as measured by higher digestive activity and improved integrity and immunity of the small intestines (SI). To test this hypothesis, piglets were removed from the sow at day 3 and fed either a pure milk replacer diet (MILK) or from day 11 a milk replacer diet with increasing levels of wheat (WHEAT). The WHEAT piglets had an increased enzyme activity of maltase and sucrase in the proximal part of the SI compared with the MILK group. There were no differences in gut morphology, histopathology and gene expression between the groups. In conclusion, the pigs given a milk replacer with added wheat displayed immunological and gut mucosal enzyme maturational changes, indicatory of adaptation towards a vegetable-based diet. This was not associated with any clinical complications, and future studies are needed to show whether this could improve responses in the subsequent weaning process.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.VETPAR.2017.03.014
Abstract: In vitro methods have been developed for the detection of anthelmintic resistance in a range of nematode species. However, the life cycle of Ascaris suum renders the commonly used egg hatch assay and larval development assay unusable. In this study we developed a combined multi-well culture and agar gel larval migration assay to test the effect of benzimidazole and tetrahydropyrimidin/imidazothiazole anthelmintics against nine isolates of A. suum collected from locations in China and Denmark. Drugs tested were thiabendazole, fenbendazole, mebendazole, levamisole, and pyrantel. The percentages of larvae that migrated to the surface of each treated and control well were used to calculate the drug concentration which inhibits 50% of the larvae migration (EC
Publisher: Elsevier BV
Date: 12-2015
Publisher: Wiley
Date: 03-12-2019
DOI: 10.1111/IMM.13151
Publisher: Springer Science and Business Media LLC
Date: 16-09-2015
DOI: 10.1038/SREP14081
Abstract: The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration and importantly assess reproducibility. Our standardized protocol involves testing each serum s le in singlicate with three independent neutrophil donors and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of s les from in iduals enrolled in immuno-epidemiological studies or clinical vaccine trials and requires only 6 μL of serum per s le. Using a cohort of 86 s les, we show that malaria-exposed in iduals induce higher ADRB activity than malaria-naïve in iduals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity and provides an important standardized cell-based assay in the field.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Hindawi Limited
Date: 10-11-2017
DOI: 10.1111/TBED.12707
Abstract: Gastrointestinal (GI) nematode control has an important role to play in increasing livestock production from a limited natural resource base and to improve animal health and welfare. In this synthetic review, we identify key research priorities for GI nematode control in farmed ruminants and pigs, to support the development of roadmaps and strategic research agendas by governments, industry and policymakers. These priorities were derived from the DISCONTOOLS gap analysis for nematodes and follow-up discussions within the recently formed Livestock Helminth Research Alliance (LiHRA). In the face of ongoing spread of anthelmintic resistance (AR), we are increasingly faced with a failure of existing control methods against GI nematodes. Effective vaccines against GI nematodes are generally not available, and anthelmintic treatment will therefore remain a cornerstone for their effective control. At the same time, consumers and producers are increasingly concerned with environmental issues associated with chemical parasite control. To address current challenges in GI nematode control, it is crucial to deepen our insights into erse aspects of epidemiology, AR, host immune mechanisms and the socio-psychological aspects of nematode control. This will enhance the development, and subsequent uptake, of the new diagnostics, vaccines, pharma-/nutraceuticals, control methods and decision support tools required to respond to the spread of AR and the shifting epidemiology of GI nematodes in response to climatic, land-use and farm husbandry changes. More emphasis needs to be placed on the upfront evaluation of the economic value of these innovations as well as the socio-psychological aspects to prioritize research and facilitate uptake of innovations in practice. Finally, targeted regulatory guidance is needed to create an innovation-supportive environment for industries and to accelerate the access to market of new control tools.
Publisher: Frontiers Media SA
Date: 24-02-2021
DOI: 10.3389/FIMMU.2021.637603
Abstract: The role of dietary components in immune function has acquired considerable attention in recent years. An important focus area is to unravel the role of bioactive dietary compounds in relation to enteric disease and their impact on gut mucosal immunity. Proanthocyanidins (PAC) are among the most common and most consumed dietary polyphenols, and are characterised by their variable molecular structures and erse bioactivities. In particular, their anti-oxidative effects and ability to modulate gut microbiota have been widely described. However, there is limited evidence on the mechanism of action of PAC on the immune system, nor is it clearly established how PAC may influence susceptibility to enteric infections. Establishing the sites of action of PAC and their metabolites within the gut environment is fundamental to determine the applicability of PAC against enteric pathogens. Some mechanistic studies have shown that PAC have direct modulatory effects on immune cell signalling, isolated pathogens, and gut mucosal barrier integrity. Boosting the recruitment of immune cells and suppressing the amount of pro-inflammatory cytokines are modulating factors regulated by PAC, and can either be beneficial or detrimental in the course of re-establishing gut homeostasis. Herein, we review how PAC may alter distinct immune responses towards enteric bacterial, viral and parasitic infections, and how the modulation of gut microbiota may act as a mediating factor. Furthermore, we discuss how future studies could help unravel the role of PAC in preventing and/or alleviating intestinal inflammation and dysbiosis caused by enteric disease.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2013
DOI: 10.1038/SREP01706
Publisher: Elsevier BV
Date: 05-2023
Publisher: Wiley
Date: 14-04-2018
DOI: 10.1111/PIM.12525
Abstract: Giardia duodenalis is a common intestinal protozoan parasite known to modulate host immune responses, including dendritic cell (DC) function. Coinfections of intestinal pathogens are common, and thus, DCs may be concurrently exposed to antigens from multiple parasites. Here, we investigated the effects of G. duodenalis products on human monocyte-derived DC function independently and in combination with helminth antigens (Ascaris suum and Trichuris suis). All antigens in idually induced an anti-inflammatory phenotype in DCs, reducing lipopolysaccharide (LPS)-induced interleukin (IL)-6, IL-12p70 and tumour necrosis factor (TNF)-α secretion. G. duodenalis and T. suis products also consistently upregulated IL-10 production. Despite a similar modulation of cytokine secretion, additive effects between Giardia and helminth products were not observed, indicating a dominant effect of a single parasite stimulus and limited interactive effects on DC function. G. duodenalis trophozoites induced rapid apoptosis in DCs, which was not observed with the helminth antigens suggesting that the modulatory effects of G. duodenalis may override that of A. suum and T. suis. Thus, G. duodenalis modulates DC activity by modulating cytokine secretion and/or inducing apoptosis, which may be a parasite-driven mechanism to d en host immunity and establish chronic infections. The differential mechanisms of DC modulation by intestinal parasites warrant further attention.
Publisher: Wiley
Date: 14-02-2019
Publisher: The American Association of Immunologists
Date: 2014
Abstract: There is intense interest in induction and characterization of strain-transcending neutralizing Ab against antigenically variable human pathogens. We have recently identified the human malaria parasite Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) as a target of broadly neutralizing Abs, but there is little information regarding the functional mechanism(s) of Ab-mediated neutralization. In this study, we report that vaccine-induced polyclonal anti-PfRH5 Abs inhibit the tight attachment of merozoites to erythrocytes and are capable of blocking the interaction of PfRH5 with its receptor basigin. Furthermore, by developing anti-PfRH5 mAbs, we provide evidence of the following: 1) the ability to block the PfRH5–basigin interaction in vitro is predictive of functional activity, but absence of blockade does not predict absence of functional activity 2) neutralizing mAbs bind spatially related epitopes on the folded protein, involving at least two defined regions of the PfRH5 primary sequence 3) a brief exposure window of PfRH5 is likely to necessitate rapid binding of Ab to neutralize parasites and 4) intact bivalent IgG contributes to but is not necessary for parasite neutralization. These data provide important insight into the mechanisms of broadly neutralizing anti-malaria Abs and further encourage anti-PfRH5–based malaria prevention efforts.
Publisher: Springer Science and Business Media LLC
Date: 31-12-2019
DOI: 10.1038/S41598-019-56619-0
Abstract: Cryptosporidium spp. are responsible for severe public health problems and livestock production losses. Treatment options are limited to only one drug available for human and bovine cryptosporidiosis, respectively, and both drugs exhibit only partial efficacy. Sesquiterpene lactones (SL) are plant bioactive compounds that function as a defence mechanism against herbivores. SL have demonstrated anti-parasitic properties against a range of parasitic taxa but knowledge about their anti- Cryptosporidium efficacy is limited. The effect of SL-rich leaf and root extracts from chicory ( Cichorium intybus cv. Spadona) was investigated using human colon adenocarcinoma (HCT-8) cells infected with Cryptosporidium parvum . C . parvum oocysts were inoculated onto the cell monolayer and i) incubated for 4 hours with extracts (leaf and root extracts 300, 150, 75, 37.5, 18.75 and 9.375 μg/mL) in triplicates followed by incubation in bioactive free media (sporozoite invasion assays) or ii) incubated for 4 hours in bioactive free media followed by 48-hours incubation with extracts (growth inhibition assays). Extract toxicity on HCT-8 cells was assessed via water-soluble tetrazolium (WST)-1 assay prior to quantifying parasitic growth via immunofluorescence. Both extracts demonstrated dose-dependent inhibition in the growth inhibition assays ( p = 0.0001 for both extracts) but not in the invasion assays. Anti-parasitic activity did not appear to be solely related to SL content, with the extract with lower SL content (leaf) exhibiting higher inhibition at 300 μg/ml. However, given the limited treatment options available for Cryptosporidium spp., our study encourages further investigation into the use of chicory extracts to identify novel active compound(s) inhibiting these protozoa.
Publisher: MDPI AG
Date: 11-04-2022
DOI: 10.3390/ANI12080989
Abstract: Weaning comprises a challenging period for pigs, but dietary tools can be implemented to avoid excess antibiotics usage. Therefore, we tested the effect of a 17.6% crude protein (CP) diet on growth and diarrhoea and investigated the effect of a 15.5% CP diet post-weaning on transcriptomic responses, growth, and diarrhoea-related antibiotic treatments. At weaning, pigs were ided into five dietary treatment groups in a three-phase diet from weaning to 30 kg bodyweight. The diets included a positive control group (PC) with medicinal zinc oxide, a negative control group (NC), a 17.6% CP diet based on soy protein concentrate (SP), a 17.6% CP diet based on soybean meal (SB), and a 15.5% CP diet with additional amino acids (XLA). Growth performance and the occurrence of diarrhoea were similar between the SP and SB groups. The XLA pigs had a reduced weight gain and fewer antibiotics treatments caused by diarrhoea, as well as a reduced level of blood proteins. Intestinal tissue s les from the XLA pigs displayed decreased expression of genes involved in nutrient metabolism and immune responses relative to the PC group. In conclusion, a very low CP diet reduces antibiotics treatments, but also adapts gut nutrient metabolism and reduces growth performance.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.TVJL.2011.10.009
Abstract: Diarrhoea is a major impediment to profitable sheep production in many countries as it predisposes animals to blowfly strike and contaminates wool and meat carcasses. While it is accepted that nematode parasites are a major cause of diarrhoea in grazing animals, less is known about what facets of the host-parasite relationship lead to diarrhoea and what the most appropriate control strategies are. In this review, the relationship between gastrointestinal nematode infection and diarrhoea is discussed and it is concluded that in many cases, particularly in immunologically mature sheep, diarrhoea is not due to parasite infection per se but rather due to immunopathological processes. Mechanisms that lead to faecal softening in immune sheep are considered, and the question addressed as to whether anthelmintic treatment and selective breeding of naturally parasite-resistant sheep will effectively reduce the occurrence of diarrhoea.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2020
DOI: 10.1038/S41598-020-61623-W
Abstract: Large litter sizes have resulted in more piglets being exposed to intrauterine growth restriction (IUGR). Growth restriction during fetal life is linked with lower growth efficiency and increased susceptibility to infections in postnatal life and IUGR may associate with an altered innate immune system. We investigated the haematological, thromboelastography and plasma biochemical profiles of IUGR and normal piglets as well as cytokine responses in peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS) at 24 days of age. Piglets were classified at birth based on their head morphology as either IUGR or normal. The present study showed a modulation of the immune function of IUGR pigs, characterized by an increase in neutrophil percentage and fibrinogen levels but a decrease in CD4+ T-cells. A lower level of LPS-induced IL-1β production was evident in IUGR pigs, suggesting immunological hypo-responsiveness. Furthermore, higher levels of reticulocytes, MCV and MCH and lower levels of erythrocytes in IUGR pigs suggest altered bone marrow hematopoiesis. All together, the results suggest a moderate suppression of the immune response of IUGR piglets, which may have implications for resistance to pathogen challenges in the post-weaning period. Serum metabolites and blood clotting profile did not differ between IUGR and normal piglets.
Publisher: American Society for Microbiology
Date: 12-2017
DOI: 10.1128/IAI.00191-17
Abstract: Epidemiological observations have linked increased host iron with malaria susceptibility, and perturbed iron handling has been hypothesized to contribute to the potentially life-threatening anemia that may accompany blood-stage malaria infection. To improve our understanding of these relationships, we examined the pathways involved in regulation of the master controller of iron metabolism, the hormone hepcidin, in malaria infection. We show that hepcidin upregulation in Plasmodium berghei murine malaria infection was accompanied by changes in expression of bone morphogenetic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway target genes, a key pathway involved in hepcidin regulation. We therefore investigated known agonists of the BMP/SMAD pathway and found that Bmp gene expression was not increased in infection. In contrast, activin B, which can signal through the BMP/SMAD pathway and has been associated with increased hepcidin during inflammation, was upregulated in the livers of Plasmodium berghei -infected mice hepatic activin B was also upregulated at peak parasitemia during infection with Plasmodium chabaudi . Concentrations of the closely related protein activin A increased in parallel with hepcidin in serum from malaria-naive volunteers infected in controlled human malaria infection (CHMI) clinical trials. However, antibody-mediated neutralization of activin activity during murine malaria infection did not affect hepcidin expression, suggesting that these proteins do not stimulate hepcidin upregulation directly. In conclusion, we present evidence that the BMP/SMAD signaling pathway is perturbed in malaria infection but that activins, although raised in malaria infection, may not have a critical role in hepcidin upregulation in this setting.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.VETPAR.2014.11.006
Abstract: Natural anti-parasitic compounds in plants such as condensed tannins (CT) have anthelmintic properties against a range of gastrointestinal nematodes, but for other helminths such effects are unexplored. The aim of this study was to assess the effects of CT from three different plant extracts in a model system employing the rat tapeworm, Hymenolepis diminuta, in its intermediate host, Tenebrio molitor. An in vitro study examined infectivity of H. diminuta cysticercoids (excystation success) isolated from infected beetles exposed to different concentrations of CT extracts from pine bark (PB) (Pinus sps), hazelnut pericarp (HN) (Corylus avellana) or white clover flowers (WC) (Trifolium repens), in comparison with the anthelmintic drug praziquantel (positive control). In the in vitro study, praziquantel and CT from all three plant extracts had dose-dependent inhibitory effects on cysticercoid excystation. The HN extract was most effective at inhibiting excystation, followed by PB and WC. An in vivo study was carried out on infected beetles (measured as cysticercoid establishment) fed different doses of PB, HN and praziquantel. There was a highly significant inhibitory effect of HN on cysticercoid development (p=0.0002). Overall, CT showed a promising anti-cestodal effect against the metacestode stage of H. diminuta.
Publisher: American Chemical Society (ACS)
Date: 30-01-2023
Publisher: MDPI AG
Date: 15-10-2022
Abstract: The garlic-derived compounds propyl propane thiosulfinate (PTS) and propyl propane thiosulfonate (PTSO) are metabolites with putative health benefits against intestinal inflammation that may be related to their antioxidant activity. However, the underlying mechanisms remain unclear, and whether PTS-PTSO can promote gut health by altering the microbiota and exert protection against enteric pathogens needs further investigation. Here, we explored the antioxidant activity of PTS-PTSO in murine macrophages in vitro, and in an in vivo model of bacterial infection with the bacterial pathogen Citrobacter rodentium. PTS-PTSO attenuated reactive oxygen species in lipopolysaccharide-stimulated macrophages in a nuclear factor erythroid factor 2-related factor 2 (Nrf2)-dependent manner, decreased nitric oxide levels both in macrophages in vitro and in the sera of mice fed PTS-PTSO, and had putatively beneficial effects on the commensal gut microbiota. Importantly, PTS-PTSO decreased faecal C. rodentium counts, concomitant with upregulation of Nrf2-related genes in colon tissue. Thus, PTS-PTSO mediates Nrf2-mediated antioxidant activity and modulates gut microbiota, which may protect the host against C. rodentium colonization. Our results provide further insight into how PTS-PTSO and related bioactive dietary compounds may reduce enteric infections.
Publisher: American Chemical Society (ACS)
Date: 14-11-2016
Abstract: Parasitic gastrointestinal nematodes (GIN) of livestock are increasingly developing resistance to synthetic nematocidal drugs. Moreover, the use of nematocides can induce ecotoxicity by affecting free-living nematodes. Condensed tannins (CT) are a structurally erse group of bioactive plant compounds possessing anthelmintic activity against GIN. We investigated the relationship between the chemical structure of contrasting, purified CT and nematocidal effects using Caenorhabditis elegans. We also explored whether the nematocidal activity of CT could synergize with trans-cinnamaldehyde (CIN). A nonsignificant correlation was evident between the ability of CT fractions to inhibit C. elegans motility and the molar proportion of prodelphinidin subunits in purified CT s les. Synergistic inhibition of motility was achieved by combinations of CT and CIN. Galloylation of procyanidins was also a key factor for synergy. To increase the nematocidal effect of CT, plant sources containing CT with specific structural features could be selected and combined with compounds acting in synergy.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.JNUTBIO.2021.108887
Abstract: Phytonutrients such as cinnamaldehyde (CA) have been studied for their effects on metabolic diseases, but their influence on mucosal inflammation and immunity to enteric infection are not well documented. Here, we show that consumption of CA in mice significantly down-regulates transcriptional pathways connected to inflammation in the small intestine, and alters T-cell populations in mesenteric lymph nodes. During infection with the enteric helminth Heligomosomoides polygyrus, CA treatment attenuated infection-induced changes in biological pathways connected to cell cycle and mitotic activity, and tended to reduce worm burdens. Mechanistically, CA did not appear to exert activity through a prebiotic effect, as CA treatment did not significantly change the composition of the gut microbiota. Instead, in vitro experiments showed that CA directly induced xenobiotic metabolizing pathways in intestinal epithelial cells and suppressed endotoxin-induced inflammatory responses in macrophages. Collectively, our results show that CA down-regulates inflammatory pathways in the intestinal mucosa and can limit the pathological response to enteric infection. These properties appear to be largely independent of the gut microbiota, and instead connected to the ability of CA to induce antioxidant pathways in intestinal cells. Our results encourage further investigation into the use of CA and related phytonutrients as functional food components to promote intestinal health in humans and animals.
Publisher: MDPI AG
Date: 22-06-2020
DOI: 10.3390/ANI10061073
Abstract: A well-balanced gut microbiome is associated with improved health outcomes, but to date, the GM of IUGR piglets have only been sparsely investigated. Here, we investigated GM composition, color of colon content, and blood parameters of 20 IUGR and 20 normal 24-day-old piglets. No significant differences were detected in colon microbiota composition between IUGR and the normal piglets with respect to alpha and beta ersity measures. The colon content of these piglets displayed three colors: brown, black, and yellow. Interestingly, the color of the colon content varied with microbial community composition, with significant differences in the relative abundance of taxa belonging to Fusobacteria and Treponema. Fusobacteria were most abundant in yellow fecal s les, with a mean relative abundance around 5.6%, whereas this was 0.51% within brown and 0.02% for the black fecal s les. Fusobacteria positively correlated with total blood protein, albumin, and triglycerides. Contrarily, Treponema was at 0.9% the most abundant in black fecal s les, while present at 0.1% of relative abundance in brown fecal s les and 0.01% in yellow s les, correlating positively with blood iron content. This study indicates that colon/fecal content color can be used as indicator for specific GM and metabolite signatures.
Publisher: MDPI AG
Date: 29-03-2023
DOI: 10.3390/PATHOGENS12040536
Abstract: Enteric helminth infection is an increasing concern in companion animals due to reports of resistance to commonly used anthelmintic drugs. Thus, the assessment of new therapeutic options such as bioactive dietary additives is of high importance. Here, we adapted egg hatch, larval migration, and larval motility assays to screen extracts of several natural ingredients against the canine hookworm Uncinaria stenocephala, a prevalent parasite of dogs in northern Europe. Egg hatch and larval migration assays were established showing that the anthelmintic drugs levamisole and albendazole had strong anti-parasitic activity against U. stenocephala, validating the use of these assays for the assessment of novel anti-parasitic substances. Subsequently, we identified that extracts from the seaweed Saccharina latissima, but not extracts from grape seed or chicory, significantly inhibited both hatching and larval migration. Finally, we showed that α-linolenic acid, a putative anti-parasitic compound from S. latissima, also exhibited anti-parasitic activity. Collectively, our results established a platform for the screening for anthelmintic resistance or novel drug candidates against U. stenocephala and highlighted the potential use of seaweed extracts as a functional food component to help control hookworm infection in dogs.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.IJPARA.2012.09.002
Abstract: The standard membrane feeding assay (SMFA) is currently considered to be the 'gold standard' for assessing the effectiveness of malaria transmission blocking interventions (TBIs) in vivo. The operation and analysis of SMFAs has varied between laboratories: field scientists often measure TBI efficacy as a reduction in the prevalence of infected mosquitoes whilst laboratory scientists are more likely to quote efficacy as a change in the number of oocysts within the mosquito. These metrics give outputs that differ widely, resulting in a need for greater understanding of how the SMFA informs TBI assessment. Using data from 536 different assays (conducted on Plasmodium falciparum and Plasmodium berghei, in either Anopheles gambiae or Anopheles stephensi) it is shown that the relationship between these metrics is complex, yet predictable. Results demonstrate that the distribution of oocysts between mosquitoes is highly aggregated, making efficacy estimates based on reductions in intensity highly uncertain. Analysis of 30 SMFAs carried out on the same TBI confirms that the observed reduction in prevalence depends upon the parasite exposure (as measured by oocyst intensity in the control group), with assays which have lower exposure appearing more effective. By contrast, if efficacy is estimated as a reduction in oocyst intensity, then this candidate demonstrated constant efficacy, irrespective of the exposure level. To report transmission-blockade efficacy accurately, the results of SMFAs should give both the prevalence and intensity of oocysts in both the control and intervention group. Candidates should be assessed against a range of parasite exposures to allow laboratory results to be extrapolated to different field situations. Currently, many studies assessing TBIs are underpowered and uncertainties in efficacy estimates rarely reported. Statistical techniques that account for oocyst over-dispersion can reduce the number of mosquitoes that need to be dissected and allow TBI candidates from different laboratories to be accurately compared.
Publisher: MDPI AG
Date: 10-11-2022
DOI: 10.3390/ANI12223112
Abstract: The aim of this study was to investigate differences in growth, hematology, metabolism, small intestine (SI) morphology, and enzyme activity of sow-reared piglets (SOW) compared to artificially reared piglets (MILK) given milk replacers in two different environments. Thirty-six piglets were selected at birth based on their birth weight eighteen were kept on a commercial farm, another eighteen transferred to an animal research facility for artificial rearing. Differences were observed in enzymatic activity, with a larger amount of sucrase in the SOW compared with MILK group across the SI. SOW piglets also had a body composition with a larger amount of fat, muscle, and bone mass content. Differences in hematology were observed, suggesting environmental influences, biochemistry differences reflective of the diets given, and finally, an increased dry matter (DM) intake in SOW piglets was estimated. No differences were observed in immune function and only small differences in the gut integrity were found between the two groups. It can be concluded that body composition and enzyme activity can be manipulated through dietary intervention and that an increase in DM during lactation is beneficial for gut function. The study warrants further investigation into what this means for the subsequent weaning period.
Publisher: Oxford University Press (OUP)
Date: 25-10-2013
DOI: 10.1189/JLB.0513274
Abstract: New tools are required to expedite the development of an effective vaccine against the blood-stage infection with the human malaria parasite Plasmodium falciparum. This work describes the assessment of the ADRB assay in a mouse model, characterizing the functional interaction between antimalarial serum antibodies and FcRs upon neutrophils. We describe a reproducible, antigen-specific assay, dependent on functional FcR signaling, and show that ADRB activity is induced equally by IgG1 and IgG2a isotypes and is modulated by blocking FcR function. However, following immunization of mice with the blood-stage vaccine candidate antigen MSP142, no measurable ADRB activity was induced against PEMS and neither was vaccine efficacy modulated against Plasmodium yoelii blood-stage challenge in γ−/− mice compared with WT mice. In contrast, following a primary, nonlethal P. yoelii parasite challenge, serum from vaccinated mice and nonimmunized controls showed anti-PEMS ADRB activity. Upon secondary challenge, nonimmunized γ−/− mice showed a reduced ability to control blood-stage parasitemia compared with immunized γ−/− mice however, WT mice, depleted of their neutrophils, did not lose their ability to control infection. Thus, whereas neutrophil-induced ADRB against PEMS does not appear to play a role in protection against P. yoelii rodent malaria, induction of ADRB activity after challenge suggests that antigen targets of anti-PEMS ADRB activity remain to be established, as well as further supporting the observation that ADRB activity to P. falciparum arises following repeated natural exposure.
Publisher: Cambridge University Press (CUP)
Date: 05-11-2018
DOI: 10.1017/S0031182018001786
Abstract: Control of equine nematodes has relied on benzimidazoles (BZs), tetrahydropyrimidines and macrocyclic lactones. The intensive use of anthelmintics has led to the development of anthelmintic resistance (AR) in equine cyathostomins and Parascaris equorum . Field studies indicate that BZ and pyrantel resistance is widespread in cyathostomins and there are also increasing reports of resistance to macrocyclic lactones in cyathostomins and P. equorum . The unavailability of reliable laboratory-based techniques for detecting resistance further augments the problem of nematode control in horses. The only reliable test used in horses is the fecal egg count reduction test therefore, more focus should be given to develop and validate improved methodologies for diagnosing AR at an early stage, as well as determining the mechanisms involved in resistance development. Therefore, equine industry and researchers should devise and implement new strategies for equine worm control, such as the use of bioactive pastures or novel feed additives, and control should increasingly incorporate alternative and evidence-based parasite control strategies to limit the development of AR. This review describes the history and prevalence of AR in equine nematodes, along with recent advances in developing resistance diagnostic tests and worm control strategies in horses, as well as giving some perspective on recent research into novel control strategies.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.VETPAR.2018.01.035
Abstract: Veterinary parasitology has always been considered to be relevant and interesting by the Danish veterinary students. Students have to acquaint themselves with many new, small creatures with complicated and varied life cycles and with intricate Latin names that are difficult to pronounce, as only a few parasites have Danish names. In our veterinary curriculum, zoology has disappeared as a discipline, and parasitology has gradually moved from the third year to the beginning of the second year, which implies that, for ex le, pathology and pharmacology are "unknown fields". The number of contact hours in veterinary parasitology has been gradually cut to 24 lectures (35 min each) and practical exercises (24 h), including 9 h on coprology. The course is taught and examined jointly with bacteriology and virology in a 8-week course. As a comprehensive course, it has become increasingly difficult to get students to acquire enough active knowledge of the most common parasites and an understanding of the basic principles in relation to, for ex le, transmission and control. Even though information is readily accessible through books and on-line resources, we still believe that a competent clinician should know a range of parasites by heart as an active resource for their work. The dilemma has been tackled (partly) by introducing a veterinary paraclinical refresher course of 18 h (half practicals and half lectures) in the fourth study year. The focus here is on host(herd)-oriented clinical and diagnostic parasitology. The students can also now select a One Health track for six months in which zoonotic parasites are obviously a relevant topic.
Publisher: Elsevier BV
Date: 2010
Publisher: Springer Science and Business Media LLC
Date: 22-08-2018
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.RVSC.2016.02.021
Abstract: Plant-derived proanthocyanidins (PAC) have been promoted as a natural method of improving health and immune function in livestock. It has previously been shown that PAC are effective agonists for activating ruminant γδ T-cells in vitro, however effects on other livestock species are not yet clear. Moreover, the fine structural characteristics of the PAC which contribute to this stimulatory effect have not been elucidated. Here, we demonstrate activation of porcine γδ T-cells by PAC via up-regulation of CD25 (IL-2Rα) and show that 1) activation is dependent on degree of polymerization (DP), with PAC fractions containing polymers with mean DP >6 significantly more effective than fractions with mean DP <6, whilst flavan-3-ol monomers (the constituent monomeric units of PAC) did not induce CD25 expression and 2) both procyanidin and prodelphinidin-type PAC are effective agonists. Furthermore, we show that this effect of PAC is restricted to the γδ T-cell population within porcine peripheral mononuclear cells as significant CD25 up-regulation was not observed in non γδ T-cells, and no activation (via CD80/86 up-regulation) was evident in monocytes. Our results show that dietary PAC may contribute to enhancement of innate immunity in swine via activation of γδ T-cells.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.IMLET.2017.06.002
Abstract: Ingestion of eggs (ova) of the porcine nematode parasite Trichuris suis (TSO) may reduce the severity of autoimmune disorders, however the development of TSO treatment as a useful therapy for autoimmune diseases is h ered by a lack of knowledge on the development of the parasite and the nature of the local immune responses in humans. Here, we used colonoscopy to investigate the development of T. suis and related mucosal and systemic immune responses during TSO treatment in an intestinally healthy male volunteer. TSO treatment induced T. suis-specific serum antibodies, a transient blood eosinophilia, and increases in IFNγ
Publisher: Springer Science and Business Media LLC
Date: 30-09-2015
DOI: 10.1038/SREP14791
Abstract: Cinnamon ( Cinnamomum verum ) has been shown to have anti-inflammatory and antimicrobial properties, but effects on parasitic worms of the intestine have not been investigated. Here, extracts of cinnamon bark were shown to have potent in vitro anthelmintic properties against the swine nematode Ascaris suum . Analysis of the extract revealed high concentrations of proanthocyanidins (PAC) and trans- cinnamaldehyde (CA). The PAC were subjected to thiolysis and HPLC-MS analysis which demonstrated that they were exclusively procyanidins, had a mean degree of polymerization of 5.2 and 21% of their inter-flavan-3-ol links were A-type linkages. Purification of the PAC revealed that whilst they had activity against A. suum , most of the potency of the extract derived from CA. Trichuris suis and Oesophagostomum dentatum larvae were similarly susceptible to CA. To test whether CA could reduce A. suum infection in pigs in vivo , CA was administered daily in the diet or as a targeted, encapsulated dose. However, infection was not significantly reduced. It is proposed that the rapid absorption or metabolism of CA in vivo may prevent it from being present in sufficient concentrations in situ to exert efficacy. Therefore, further work should focus on whether formulation of CA can enhance its activity against internal parasites.
Publisher: Elsevier BV
Date: 2019
Abstract: An elicitation exercise was conducted to collect and identify pressing questions concerning the study of helminths in livestock, to help guide research priorities. Questions were invited from the research community in an inclusive way. Of 385 questions submitted, 100 were chosen by online vote, with priority given to open questions in important areas that are specific enough to permit investigation within a focused project or programme of research. The final list of questions was ided into ten themes. We present the questions and set them briefly in the context of the current state of knowledge. Although subjective, the results provide a snapshot of current concerns and perceived priorities in the field of livestock helminthology, and we hope that they will stimulate ongoing or new research efforts.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.VETPAR.2010.02.033
Abstract: Sheep that are highly resistant to parasitic nematodes can suffer bad diarrhoea due to the inflammation associated with rejection of ingested larvae from pasture. We hypothesised that challenging parasite-resistant sheep indoors with nematode larvae would result in reduced faecal dry matter, and that faecal dry matter would be lowest in sheep challenged with a mixture of Trichostrongylus colubriformis and Teladorsagia circumcincta compared to those challenged with either species alone. We also hypothesised that inflammatory cells and serum antibodies and interleukin-5 would be highest in those sheep that received the mixed larval challenge. We found that faecal dry matter was reduced (P<0.05) in challenged sheep compared to unchallenged sheep, with the fastest reduction being in those sheep challenged with only Tric. colubriformis. At 14 and 23 days after challenge began, there were no differences in faecal dry matter between the three challenged groups. Within the abomasum, there were no differences in inflammatory cell numbers between unchallenged sheep and those challenged only with Tric. colubriformis. Cell numbers in sheep challenged with Tela. circumcincta were higher (P<0.05) than those in unchallenged sheep, but there were no differences between sheep challenged only with Tela. circumcincta or as a mixed challenge. In the small intestine, inflammatory cell numbers were higher (P<0.05) in sheep that received the mixed challenge compared to controls. Cell numbers in sheep challenged with either Tela. circumcincta or Tric. colubriformis were also slightly higher than those in controls. Larval challenge increased (P<0.05) levels of IgA and IgE in serum, but there were no differences between the three challenged groups. Larval challenge also increased (P<0.05) levels of IL-5, with the greatest increase being in those sheep challenged with both species. We concluded that both Tela. circumcincta and Tric. colubriformis can cause immune-mediated diarrhoea in sheep, and that a mixed challenge will not necessarily lead to worse diarrhoea or higher concentrations of antibodies in serum. We also concluded that challenge with Tric. colubriformis leads to no inflammation in the abomasum, but challenge with Tela. circumcincta may lead to some inflammation in the small intestine.
Publisher: Frontiers Media SA
Date: 05-01-2022
DOI: 10.3389/FIMMU.2021.793260
Abstract: Dietary probiotics may enhance gut health by directly competing with pathogenic agents and through immunostimulatory effects. These properties are recognized in the context of bacterial and viral pathogens, but less is known about interactions with eukaryotic pathogens such as parasitic worms (helminths). In this study we investigated whether two probiotic mixtures (comprised of Bacillus amyloliquefaciens, B. subtilis , and Enterococcus faecium [BBE], or Lactobacillus rhamnosus LGG and Bifidobacterium animalis subspecies Lactis Bb12 [LB]) could modulate helminth infection kinetics as well as the gut microbiome and intestinal immune responses in pigs infected with the nodular worm Oesophagostomum dentatum . We observed that neither probiotic mixture influenced helminth infection levels. BBE, and to a lesser extent LB, changed the alpha- and beta- ersity indices of the colon and fecal microbiota, notably including an enrichment of fecal Bifidobacterium spp. by BBE. However, these effects were muted by concurrent O. dentatum infection. BBE (but not LB) significantly attenuated the O. dentatum -induced upregulation of genes involved in type-2 inflammation and restored normal lymphocyte ratios in the ileo-caecal lymph nodes that were altered by infection. Moreover, inflammatory cytokine release from blood mononuclear cells and intestinal lymphocytes was diminished by BBE. Collectively, our data suggest that selected probiotic mixtures can play a role in maintaining immune homeostasis during type 2-biased inflammation. In addition, potentially beneficial changes in the microbiome induced by dietary probiotics may be counteracted by helminths, highlighting the complex inter-relationships that potentially exist between probiotic bacteria and intestinal parasites.
Publisher: Wiley
Date: 14-12-2016
DOI: 10.1111/PIM.12394
Abstract: Helminthic therapy of immune-mediated diseases has gained attention in recent years, but we know little of how helminths modulate human immunity. In this study, we investigated how self-infection with Trichuris (T.) trichiura in an adult man without intestinal disease affected mucosal and systemic immunity. Colonic mucosal biopsies were obtained at baseline, during T. trichiura infection, and after its clearance following mebendazole treatment. Unexpectedly, the volunteer experienced a C ylobacter colitis following T. trichiura clearance, and this served as a positive infectious control. Trichuris trichiura colonization induced equally increased expressions of T-helper (h)1-, Th2-, Th17- and Treg-associated cytokines and transcription factors, measured by quantitative polymerase chain reaction. We observed several indicators of modulation of systemic immunity during the T. trichiura infection. Plasma eosinophils and anti-Trichuris antibodies rose markedly during the inoculation phase, and a shift towards a Th2-dominated T cell response at the expense of the Th1-response was observed in circulating T cells. Taken together, our findings corroborate that helminths modulate regional and systemic human immunity.
Publisher: Public Library of Science (PLoS)
Date: 13-10-2017
Publisher: Wiley
Date: 06-06-2023
DOI: 10.1111/PIM.12998
Abstract: Intestinal tuft cells have been shown to induce type 2 immune responses during viable parasite infections, but whether oral supplementation with a parasitic exudate is able to promote type 2 immune responses that have been shown to positively regulate obesogenic metabolic processes is yet unresolved. High‐fat fed mice were gavaged with pseudocoelomic fluid (PCF) derived from the helminth Ascaris suum or saline thrice a week during weeks 5–9, followed by examination of intestinal tuft cell activity, immune, and metabolic parameters. Helminth PCF upregulated expression of distinct genes in small intestinal tuft cells, including genes involved in regulation of RUNX1 and organic cation transporters. Helminth PCF also enhanced levels of innate lymphoid cells in the ileum, and eosinophils in epididymal white adipose tissue (eWAT). Network analyses revealed two distinct immunometabolic cues affected by oral helminth PCF in high‐fat fed mice: one coupling the small intestinal tuft cell responses to the fat‐to‐lean mass ratio and a second coupling eosinophils in eWAT to general regulation of body fat mass. Our findings point to specific mechanisms by which oral supplementation with helminth PCF may translate into systems‐wide effects linking to reduced body and fat mass gain in mice during high‐fat feeding.
Publisher: Cambridge University Press (CUP)
Date: 02-2011
DOI: 10.1017/S0031182010001769
Abstract: As Rhagodia preissii had shown significant in vitro anthelmintic activity in a previous study, we examined the effect of including this shrub in the diet of sheep infected with Trichostrongylus colubriformis . Worm-infected merino wethers were grazed for 7 weeks on either R. preissii or annual pasture, and faecal egg counts (FECs) were conducted weekly. Plant material was collected weekly from eaten and uneaten plants, and analysed for levels of plant secondary metabolites (tannins, oxalates, saponins) and in vitro anthelmintic activity. While mean FECs were consistently lower in sheep grazing R. preissii compared to pasture (reductions of 20–74%), the differences were not significant. There was no relationship between grazing preference (eaten or uneaten) and in vitro anthelmintic activity of plant extracts. The levels of saponins and oxalates did not correlate with grazing preference or in vitro anthelmintic activity, while tannins were not responsible for the anthelmintic activity. While the identity of the grazing deterrent and in vitro anthelmintic compounds remain unknown, the presence of plants which were both highly preferred by the sheep and showed in vitro anthelmintic activity indicates a potential to develop the species as an anthelmintic shrub through selection of shrub populations dominated by such plants.
Publisher: Wiley
Date: 05-2019
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.VETIMM.2019.03.012
Abstract: Helminth parasites are highly prevalent in swine production, causing chronic infections and considerable morbidity due to growth retardation. Moreover, helminths actively modulate host immune responses to other pathogens and/or vaccines. Here, we investigated the modulatory effects of Ascaris suum adult body fluid (ABF) and Trichuris suis Soluble Products (TsSP) on the cytokine response in porcine peripheral blood mononuclear cells (PBMCs) and the intestinal epithelial cell line IPEC-J2. In PBMCs, TsSP induced the secretion of IL-6, IL-10 and IL-1β, but not TNF-α. Moreover, TsSP significantly enhanced the production of bacterial lipopolysaccharide (LPS)-induced IL-6 and IL-10 but suppressed the production of LPS-induced TNF-α. ABF did not induce cytokine secretion from PBMC, but suppressed LPS-induced secretion of TNF-α and IL-6. ABF did not have any effect on cytokine production in IPEC-J2 cells. In contrast, TsSP selectively induced the secretion of IL-6, and enhanced the IL-6 response induced by LPS. The IL-6 response appeared to be a conserved response to T. suis products, as significant secretion was also observed in alveolar macrophages. Thus, T. suis products have erse modulatory effects on cytokine secretion in vitro, with IL-6 production a consistent feature of the innate host response.
Publisher: Elsevier BV
Date: 05-2023
Publisher: Elsevier BV
Date: 12-2015
Publisher: Wiley
Date: 07-03-2022
Abstract: Scope : Garlic is a source of bioactive phytonutrients that may have anti‐inflammatory or immunomodulatory properties. The mechanism(s) underlying the bioactivity of these compounds and their ability to regulate responses to enteric infections remains unclear. Methods and Results : This study investigates if a garlic‐derived preparation (PTSO‐PTS) containing two organosulfur metabolites, propyl‐propane thiosulfonate (PTSO), and propyl‐propane thiosulfinate (PTS), regulate inflammatory responses in murine macrophages and intestinal epithelial cells (IEC) in vitro, as well as in a model of enteric parasite‐induced inflammation. PTSO‐PTS decreases lipopolysaccharide‐induced secretion of TNFα, IL‐6, and IL‐27 in macrophages. RNA‐sequencing demonstrates that PTSO‐PTS strongly suppresses pathways related to immune and inflammatory signaling. PTSO‐PTS induces the expression of a number of genes involved in antioxidant responses in IEC during exposure to antigens from the parasite Trichuris muris . In vivo, PTSO‐PTS does not affect T. muris establishment or intestinal T‐cell responses but significantly alters cecal transcriptomic responses. Notably, a reduction in T. muris ‐induced expression of Tnf , Saa2 , and Nos2 is observed. Conclusion : Garlic‐derived organosulfur compounds exert anti‐inflammatory effects in macrophages and IEC, and regulate gene expression during intestinal infection. These compounds and related organic molecules may thus hold potential as functional food components to improve gut health in humans and animals.
Publisher: Wiley
Date: 30-11-2016
DOI: 10.1111/IMM.12687
Publisher: EDP Sciences
Date: 2016
Publisher: Cambridge University Press (CUP)
Date: 28-01-2011
DOI: 10.1017/S0031182010001654
Abstract: Nematode parasitism is a severe impediment to sustainable and profitable sheep production in many countries in the world. Parasite resistance to anthelmintic treatment and consumer demand for organic agricultural products has led to much research into harnessing natural immunity as a long-term control measure. However, there is evidence that many of the clinical signs of nematode infection in sheep are due to immune-mediated pathology rather than direct effects of the parasite. Therefore, the desirability of promoting a strong natural immunity in sheep has been questioned. This review attempts to clarify some of the arguments for and against promoting strong natural immunity, particularly through selective breeding of parasite-resistant animals. It is concluded that the detrimental effects of immune-mediated pathology are outweighed by epidemiological and welfare benefits. Thus, control of nematode parasites through selection of naturally resistant sheep is a sustainable and desirable objective.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.VETPAR.2010.03.031
Abstract: Immune-mediated scouring due to ingested parasite larvae is a major concern for sheep producers in Mediterranean climates. We investigated immune-mediated scouring in parasite-resistant Merino sheep in Australia. Forty-adult, parasite-resistant Merino rams were judged to be either susceptible or non-susceptible to immune-mediated scouring on the basis of dag scores taken under field conditions. We hypothesised that the susceptible rams would have lower faecal dry matter during larval challenge than non-susceptible rams and that, at post-mortem examination, inflammatory mediators and granulocytes would be negatively correlated with both faecal dry matter and worm numbers. In pens, the rams received a dose of 500 Teladorsagia circumcincta L(3) and 500 Trichostrongylus colubriformis L(3) each day for 6 weeks before euthanasia. Ten rams acted as unchallenged controls. Challenging sheep with larvae reduced faecal dry matter at 2, 3 and 4 weeks after challenge began and the greatest reductions were with the sheep susceptible to scouring. The sheep showed good resistance to the parasite challenge as evidenced by low faecal worm egg counts and low total worm counts at post-mortem, with the numbers of T. colubriformis particularly low. Sheep with low faecal dry matter had significantly higher numbers of eosinophils in small intestine tissue. Sheep with low total worm counts had significantly higher levels of bradykinin in abomasum mucus. Sheep with more granulocytes in tissue and inflammatory mediators in mucus tended to have fewer numbers of T. circumcincta but there was little relationship with numbers of T. colubriformis. Our results show that dag scores are correlated to a reduction in faecal dry matter, which can be attributed to the challenge with infective parasite larvae. Inflammation during worm infection is associated with rejection of the worm challenge and may result in more fluid faeces and consequently diarrhoea. Therefore, sheep breeders should focus on breeding for both low worm egg counts and also low dag scores.
Publisher: American Society of Parasitologists
Date: 06-2015
DOI: 10.1645/14-714.1
Abstract: Trichuris suis is a common parasitic helminth of pigs. As with many other parasites, T. suis ensures its own survival by evading host immune responses, but little is known about how this is achieved. MicroRNAs (miRNA) have been shown to be involved in various immunological processes by post-transcriptional regulation of specific genes, and the potential of using these molecules as biomarkers of disease is currently being examined. It has recently been shown that parasites may secrete extracellular structures such as exosomes and microvesicles, containing proteins and miRNA. The fusion of these structures with host cells has been demonstrated, and a role of exosome-derived miRNA in host gene regulation has been suggested. In the present study, we show that exosome- and microvesicular-like structures are secreted by T. suis L1 larvae and also demonstrate the presence of miRNA-sized RNA inside these structures. A potential role of these molecules in host-parasite interactions is suggested. In addition, an electron-dense layer covering the surface of the larvae was observed, which may play a function in host immune evasion.
Publisher: Public Library of Science (PLoS)
Date: 08-11-2012
Publisher: CSIRO Publishing
Date: 2010
DOI: 10.1071/AN09142
Abstract: In this study we test the hypothesis that selecting sheep for a low behavioural reactivity to stressful situations will improve their metabolic efficiency, and thereby feed efficiency, during a controlled trial in an animal house. Twenty-four Merino wethers were used, 12 each from lines selected for high (HBR) and low (LBR) behavioural reactivity to stressful stimuli (human presence and social isolation). The sheep were habituated to the experimental procedures for 10 days, followed by 45 days during which voluntary feed intake was measured so that total daily energy intake was quantified. The sheep were weighed twice weekly before daily feeding. Feed efficiency was determined by measuring net feed intake, average daily weight gain and body condition score. Our hypothesis was not supported by the results of this study. There was no difference between LBR and HBR sheep in average daily weight gain or body condition score. The net feed intake of HBR sheep was lower than that of LBR sheep (P = 0.02), indicating that under the conditions of our experiment, HBR sheep were actually more feed efficient than LBR sheep. This study was carried out on sheep with steady intakes and in familiar surroundings. It is possible that LBR sheep may be more efficient than HBR sheep in more stressful situations.
Publisher: Public Library of Science (PLoS)
Date: 18-06-2013
Publisher: CSIRO Publishing
Date: 2010
DOI: 10.1071/AN09144
Abstract: Immune-mediated scouring in sheep is a mucosal hypersensitivity response caused by ingesting infective parasite larvae. In this experiment we tested the hypothesis that levels of parasite-specific antibodies and also interleukin-5 (IL-5) would be negatively correlated with worm numbers, but also faecal dry matter (FDM), in parasite-resistant Merino sheep. Forty Merino rams were challenged with Trichostrongylus colubriformis and Teladorsagia circumcincta larvae every day for 6 weeks, after which they were euthanised and total worm burdens determined. Faecal s les were taken for measurement of worm egg counts and FDM. Serum was collected from the rams before and after the larval challenge commenced, and levels of ovine immunoglobulin light chain, IgG, IgM, IgA and IgE specific for T. colubriformis and T. circumcincta as well as IL-5 were determined by sandwich enzyme-linked immunosorbent assay. IL-5 and all serum antibodies apart from T. colubriformis-specific light chain were significantly increased by the larval challenge. However, none of the antibodies, or IL-5, was correlated with FDM. Negative correlations were observed between the number of adult T. circumcincta and antibody levels however, there was little relationship between antibodies and numbers of T. colubriformis. It was concluded that serum antibody levels are a poor indicator of the susceptibility of sheep to immune-mediated scouring. Because of these results, sheep breeders should continue to select for low worm egg count and focus on phenotypic indicators of scouring, such as dags, as a means to reduce diarrhoea.
Publisher: Public Library of Science (PLoS)
Date: 10-2021
DOI: 10.1371/JOURNAL.PONE.0258207
Abstract: The rapid evolution of antibiotic resistance in Clostridioides difficile and the consequent effects on prevention and treatment of C . difficile infections (CDIs) are matters of concern for public health. Thioridazine, a compound belonging to the phenothiazine group, has previous shown antimicrobial activity against C . difficile . The purpose of this present study was to investigate the potential of a novel phenothiazine derivative, JBC 1847, as an oral antimicrobial for treatment of intestinal pathogens and CDIs. The minimal inhibition concentration and the minimum bactericidal concentration of JBC 1847 against C . difficile ATCC 43255 were determined 4 μg/mL and high tolerance after oral administration in mice was observed (up to 100 mg/kg bodyweight). Pharmacokinetic modeling was conducted in silico using GastroPlus TM , predicting low ( 10%) systemic uptake after oral exposure and corresponding low C max in plasma. Impact on the intestinal bacterial composition after four days of treatment was determined by 16s rRNA MiSeq sequencing and revealed only minor impact on the microbiota in non-clinically affected mice, and there was no difference between colony-forming unit (CFU)/gram fecal material between JBC 1847 and placebo treated mice. The cytotoxicity of the compound was assessed in Caco-2 cell-line assays, in which indication of toxicity was not observed in concentrations up to seven times the minimal bactericidal concentration. In conclusion, the novel phenothiazine derivative demonstrated high antimicrobial activity against C . difficile , had low predicted gastrointestinal absorption, low intestinal ( in vitro ) cytotoxicity, and only induced minor changes of the healthy microbiota, altogether supporting that JBC 1847 could represent a novel antimicrobial candidate. The clinical importance hereof calls for future experimental studies in CDI models.
Publisher: Frontiers Media SA
Date: 12-10-2018
Publisher: Springer Science and Business Media LLC
Date: 11-06-2015
DOI: 10.1038/SREP11193
Abstract: Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected in idual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63 and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25 and Pfs48/45 were generated. Antibody responses primed in idually against all antigens by ChAd63 immunization in BALB/c mice were boosted by the administration of MVA expressing the same antigen. These antibodies exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with anti-Pfs230-C and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first head-to-head comparative analysis of leading antigens using two different parasite sources in two different vector species and can be used to guide selection of TBVs for future clinical development using the viral-vectored delivery platform.
Publisher: Wiley
Date: 02-11-2016
Publisher: Frontiers Media SA
Date: 04-03-2020
Publisher: Elsevier BV
Date: 06-2023
Publisher: Wiley
Date: 08-2021
DOI: 10.1002/JEV2.12131
Abstract: Emerging evidence suggests that immune cells not only communicate with each other through cytokines, chemokines, and cell surface receptors, but also by releasing small membranous structures known as extracellular vesicles (EVs). EVs carry a variety of different molecules that can be taken up by recipient cells. Parasitic worms are well known for their immunomodulatory properties, but whether they can affect immune responses by altering EV‐driven communication between host immune cells remains unclear. Here we provide evidence that stimulation of bone marrow‐derived macrophages (BMDMs) with soluble products of Trichuris suis (TSPs), leads to the release of EVs with anti‐inflammatory properties. Specifically, we found that EVs from TSP‐pulsed BMDMs, but not those from unstimulated BMDMs can suppress TNFα and IL‐6 release in LPS‐stimulated BMDMs and BMDCs. However, no polarization toward M1 or M2 was observed in macrophages exposed to EVs. Moreover, EVs enhanced reactive oxygen species (ROS) production in the exposed BMDMs, which was associated with a deregulated redox homeostasis as revealed by pathway analysis of transcriptomic data. Proteomic analysis identified cytochrome p450 (CYP450) as a potential source of ROS in EVs from TSP‐pulsed BMDMs. Finally, pharmacological inhibition of CYP450 activity could suppress ROS production in those BMDMs. In summary, we find that TSPs can modulate immune responses not only via direct interactions but also indirectly by eliciting the release of EVs from BMDMs that exert anti‐inflammatory effects on recipient cells.
Publisher: Springer Science and Business Media LLC
Date: 19-11-2014
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.IMBIO.2017.11.003
Abstract: Parasitic worms (helminths) are known to actively modulate host immune responses and inflammation. The aim of this study was to investigate if adult body fluid (ABF) from the helminth Ascaris suum has immunomodulatory effects on different subtypes of human monocyte-derived macrophages (Mɸ) in vitro. Mɸs were exposed to A. suum ABF at different stages of their differentiation and/or polarization. Mɸ were first differentiated from monocytes into either uncommitted (M-), classically activated (M(GM-CSF)) or alternatively activated (M(M-CSF)) phenotypes and then stimulated with lipopolysaccharide (LPS). ABF strongly suppressed LPS-induced TNF-α, IL-6 and IL-10 secretion in M(GM-CSF)s, however in M(M-CSF)s only TNF-α was suppressed, with these cells secreting high levels of IL-10 which was not affected by ABF treatment. To determine if ABF modulated the differentiation of previously uncommitted Mɸ to either type 1 or type 2 Mɸ, monocytes were differentiated with human serum into (M-)s and then polarized by IFN-γ/LPS or IL-4 treatment in the presence of ABF. Under these conditions, ABF did not modulate cytokine secretion but did reduce CD80 expression in IFNγ/LPS-polarized cells but not IL-4-polarized cells. Finally, we demonstrate that when monocytes are differentiated into M(GMCSF)s in the presence of ABF, subsequent inflammatory responses are markedly suppressed. Our data suggest that ABF inhibits cytokine secretion and co-stimulatory molecule expression in classically activated Mɸ but not in alternatively activated Mɸ, indicating selective action of ABF depending on Mɸ subtype. Moreover, ABF appears to exert stronger activity when acting upon Mɸ that have already been polarized to the type 1 phenotype, rather than influencing the polarization process per se.
Publisher: Springer Science and Business Media LLC
Date: 29-01-2021
DOI: 10.1186/S12917-021-02752-W
Abstract: Increasing evidence suggests that nutritional manipulation of the commensal gut microbiota (GM) may play a key role in maintaining animal health and production in an era of reduced antimicrobial usage. Gastrointestinal helminth infections impose a considerable burden on animal performance, and recent studies suggest that infection may substantially alter the composition and function of the GM. Here, we discuss the potential interactions between different bioactive dietary components (prebiotics, probiotics and phytonutrients) and helminth infection on the GM in livestock. A number of recent studies suggest that host diet can strongly influence the nature of the helminth-GM interaction. Nutritional manipulation of the GM may thus impact helminth infection, and conversely infection may also influence how the GM responds to dietary interventions. Moreover, a dynamic interaction exists between helminths, the GM, intestinal immune responses, and inflammation. Deciphering the mechanisms underlying the diet-GM-helminth axis will likely inform future helminth control strategies, as well as having implications for how health-promoting feed additives, such as probiotics, can play a role in sustainable animal production.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.VETPAR.2017.07.008
Abstract: Chicory shows great promise as an anthelmintic forage for grazing ruminants that can reduce reliance on anti-parasitic drugs. Recently, we reported potent anthelmintic effects of chicory-based diets in infected cattle with significant reductions in worm burdens of the abomasal nematode Ostertagia ostertagi, whilst no apparent activity was observed against the small intestinal parasite Cooperia oncophora. To explore this discrepancy, we investigated direct anthelmintic effects of forage chicory against C. oncophora in vitro. Chicory leaves (cultivar 'Spadona') were extracted with methanol in a Soxhlet apparatus and the resulting extract was purified by solid-phase extraction to concentrate bioactive phytochemicals such as sesquiterpene lactones. C. oncophora eggs and adult worms from mono-infected donor calves were exposed to decreasing concentrations of the chicory extract. In an egg hatch assay, the chicory extract induced a marked and dose-dependent inhibition of egg hatching, with 95% inhibition at 2500μg extract/mL (EC
Publisher: Elsevier BV
Date: 04-2020
Publisher: MDPI AG
Date: 06-2023
DOI: 10.3390/ANI13111851
Abstract: The objective was to study the effects of weaning in week 5 (W5) vs. week 4 (W4), as well as liquid (LF) vs. dry feed (DF), on growth performance, disaccharidase activity and nutrient transporter expression after weaning. The experiment included 12,923 pigs fed LF or DF in the pre-weaning period and a subpopulation of 15 pigs from each group, W4DF, W4LF, W5DF and W5LF, which were weighed and euthanized five days after weaning. The proximal part of the small intestine was analyzed for maltase, lactase and sucrase activity and the expression of SGLT-1, GLUT-2 and PepT-1. Pigs fed LF displayed less maltase activity (2100 vs. 2729 U/mg protein, p 0.05) but an increased expression of SGLT-1 (∆Ct: 5.22 vs. 6.21, p = 0.01). Pigs weaned in W5 were heavier than those weaned in W4 (9.35 vs. 7.11 kg BW, p ≤ 0.05), and pigs fed LF were heavier than those fed DF (8.55 vs. 7.91 kg BW, p ≤ 0.05) five days after weaning in the subpopulation. LF pigs (21.8 kg) were heavier than DF pigs (20.6 kg) (SE 0.108, p 0.0001), and W4 pigs (21.0 kg) were lighter than W5 pigs (21.5 kg) (SE 0.108, p = 0.01) at nine weeks. LF increased weight gain in the early post-weaning period and at nine weeks, although this was apparently not explained by accelerated gut maturation.
Publisher: Frontiers Media SA
Date: 02-06-2021
DOI: 10.3389/FPHAR.2021.674520
Abstract: Widespread use of antimicrobial drugs has led to high levels of drug-resistance in pathogen populations and a need for novel sources of anti-bacterial and anti-parasitic compounds. Macroalgae (seaweed) are potentially a rich source of bioactive compounds, and several species have traditionally been used as vermifuges. Here, we investigated the anti-parasitic properties of four common cold-water Nordic seaweeds Palmaria palmata (Rhodophyta), Laminaria digitata , Saccharina latissima and Ascophyllum nodosum (Ochrophyta, Phaeophyceae). Screening of organic extracts against helminths of swine ( Ascaris suum ) and sheep ( Teladorsagia circumcincta ) revealed that S. latissima and L. digitata had particularly high biological activity. A combination of molecular networking and bio-guided fractionation led to the isolation of six compounds from extracts of these two species identified in both fermented and non-fermented s les. The six isolated compounds were tentatively identified by using MS-FINDER as five fatty acids and one monoglyceride: Stearidonic acid ( 1 ), Eicosapentaenoic acid ( 2 ), Alpha-Linolenic acid ( 3 ), Docosahexaenoic acid ( 4 ), Arachidonic acid ( 5 ), and Monoacylglycerol (MG 20:5) ( 6 ). In idual compounds showed only modest activity against A. suum , but a clear synergistic effect was apparent when selected compounds were tested in combination. Collectively, our data reveal that fatty acids may have a previously unappreciated role as natural anti-parasitic compounds, which suggests that seaweed products may represent a viable option for control of intestinal helminth infections.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2013
End Date: 2016
Funder: Danish Ministry of Higher Education and Science
View Funded ActivityStart Date: 2012
End Date: 2016
Funder: Danish Ministry of Higher Education and Science
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End Date: 2017
Funder: Danish Agency for Science and Higher Education
View Funded ActivityStart Date: 2015
End Date: 2015
Funder: Danish Agency for Science and Higher Education
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Danish Agency for Science and Higher Education
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