ORCID Profile
0000-0002-5079-2857
Current Organisations
University of Cambridge
,
Australian National University
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Virology | Microbiology |
Expanding Knowledge in the Biological Sciences | Infectious Diseases
Publisher: BMJ
Date: 23-08-2018
DOI: 10.1136/INJURYPREV-2016-042151
Abstract: To curb high rates of alcohol-related violence and injury in Indigenous communities, alcohol management plans (AMPs) were implemented in 2002-2003 and tightened in 2008. This project compares injury presentations and alcohol involvement from two Indigenous Cape York communities, one that entered full prohibition and one that did not. Aclinical file audit was performed for the period 2006-2011, capturing changes in alcohol availability. Medical files were searched for injury presentation documenting type of injury, cause of injury (including alcohol), date of injury and outcomes of all presenting injuries for the time period 1 January 2006 to 31 December 2011, capturing the major changes of the 2008 AMP restrictions. Findings indicated injury presentation rates were higher in both communities before prohibition than afterwards andreduction was more pronounced in community 2 (prohibition). Ongoing research is imperative, as this area is characterised by a near-absence of evidence.
Publisher: Hindawi Limited
Date: 20-01-2021
DOI: 10.1111/CMI.13309
Abstract: Inflammasomes are cytosolic innate immune complexes, which assemble in mammalian cells in response to microbial components and endogenous danger signals. A major family of inflammasome activators is bacterial toxins. Inflammasome sensor proteins, such as the nucleotide-binding oligomerisation domain-like receptor (NLR) family members NLRP1b and NLRP3, and the tripartite motif family member Pyrin
Publisher: Elsevier BV
Date: 08-2023
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.TIM.2015.03.009
Abstract: Esophageal adenocarcinoma develops through a cascade of cellular changes that shares similarities to the etiology of Helicobacter pylori-associated intestinal-type gastric adenocarcinoma. While host genetics and immune response have been implicated in the progression to esophageal adenocarcinoma, studies investigating esophageal microbial communities suggest that bacteria may also play an important role in driving the inflammation that leads to disease. Of these, emerging C ylobacter species have been found to be more prevalent and abundant in patients progressing through the esophageal adenocarcinoma cascade compared to controls. Given that these bacteria possess several virulence mechanisms such as toxin production, cellular invasion, and intracellular survival, emerging C ylobacter species should be investigated as etiological agents of the chronic esophageal inflammation that leads to cancer.
Publisher: Springer Science and Business Media LLC
Date: 08-10-2018
Publisher: The American Association of Immunologists
Date: 15-11-2013
Abstract: Nucleotide-binding oligomerization domain–like receptors (NLRs) detect pathogens and danger-associated signals within the cell. Salmonella enterica serovar Typhimurium, an intracellular pathogen, activates caspase-1 required for the processing of the proinflammatory cytokines, pro–IL-1β and pro–IL-18, and pyroptosis. In this study, we show that Salmonella infection induces the formation of an apoptosis-associated specklike protein containing a CARD (ASC)–Caspase-8–Caspase-1 inflammasome in macrophages. Caspase-8 and caspase-1 are recruited to the ASC focus independently of one other. Salmonella infection initiates caspase-8 proteolysis in a manner dependent on NLRC4 and ASC, but not NLRP3, caspase-1 or caspase-11. Caspase-8 primarily mediates the synthesis of pro-IL-1β, but is dispensable for Salmonella-induced cell death. Overall, our findings highlight that the ASC inflammasome can recruit different members of the caspase family to induce distinct effector functions in response to Salmonella infection.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.CHOM.2022.03.003
Abstract: The gasdermin family of cell death executor proteins are activated by different proteases under different physiological conditions. A recent study by Deng et al. in Nature revealed that the cysteine protease SpeB from the human pathogen Streptococcus pyogenes directly cleaves and activates Gasdermin A to induce pyroptosis in skin cells.
Publisher: Informa UK Limited
Date: 23-03-2017
Publisher: Springer Science and Business Media LLC
Date: 12-2016
DOI: 10.1038/NATURE20597
Publisher: Wiley
Date: 12-05-2022
DOI: 10.1111/IMCB.12554
Abstract: To control infections phagocytes can directly kill invading microbes. Macrophage‐expressed gene 1 (Mpeg1), a pore‐forming protein sometimes known as perforin‐2, is reported to be essential for bacterial killing following phagocytosis. Mice homozygous for the mutant allele Mpeg1 tm1Pod succumb to bacterial infection and exhibit deficiencies in bacterial killing in vitro . Here we describe a new Mpeg mutant allele Mpeg1 tm1.1Pib on the C57BL/6J background. Mice homozygous for the new allele are not abnormally susceptible to bacterial or viral infection, and irrespective of genetic background show no perturbation in bacterial killing in vitro . Potential reasons for these conflicting findings are discussed. In further work, we show that cytokine responses to inflammatory mediators, as well as antibody generation, are also normal in Mpeg1 tm1.1Pib/tm1.1Pib mice. We also show that Mpeg1 is localized to a CD68‐positive endolysosomal compartment, and that it exists predominantly as a processed, two‐chain disulfide‐linked molecule. It is abundant in conventional dendritic cells 1, and mice lacking Mpeg1 do not present the model antigen ovalbumin efficiently. We conclude that Mpeg1 is not essential for innate antibacterial protection or antiviral immunity, but may play a focused role early in the adaptive immune response.
Publisher: Elsevier BV
Date: 03-2022
Publisher: Springer Science and Business Media LLC
Date: 20-10-2015
DOI: 10.1038/CR.2015.124
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.CHOM.2016.02.015
Abstract: Type I interferons have diametric roles in the host defense against pathogens. In this issue of Cell Host & Microbe, Castiglia et al. (2016) demonstrate that type I interferons produced during Streptococcus pyogenes infection are required to prevent inflammation-associated tissue damage and host lethality driven by the pro-inflammatory cytokine IL-1β.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2020
Publisher: Microbiology Society
Date: 18-08-2021
DOI: 10.1099/JGV.0.001638
Abstract: Viperin is a gene with a broad spectrum of antiviral functions and various mechanisms of action. The role of viperin in herpes simplex virus type 1 (HSV-1) infection is unclear, with conflicting data in the literature that is derived from a single human cell type. We have addressed this gap by investigating viperin during HSV-1 infection in several cell types, spanning species and including immortalized, non-immortalized and primary cells. We demonstrate that viperin upregulation by HSV-1 infection is cell-type-specific, with mouse cells typically showing greater increases compared with those of human origin. Further, overexpression and knockout of mouse, but not human viperin significantly impedes and increases HSV-1 replication, respectively. In primary mouse fibroblasts, viperin upregulation by infection requires viral gene transcription and occurs in a predominantly IFN-independent manner. Further we identify the N-terminal domain of viperin as being required for the anti-HSV-1 activity. Interestingly, this is the region of viperin that differs most between mouse and human, which may explain the apparent species-specific activity against HSV-1. Finally, we show that HSV-1 virion host shutoff (vhs) protein is a key viral factor that antagonises viperin in mouse cells. We conclude that viperin can be upregulated by HSV-1 in mouse and human cells, and that mouse viperin has anti-HSV-1 activity.
Publisher: American Society of Hematology
Date: 13-11-2019
Publisher: Springer Science and Business Media LLC
Date: 04-07-2013
Publisher: Springer Science and Business Media LLC
Date: 08-02-2011
Abstract: Crohn's disease is widely regarded as a multifactorial disease, and evidence from human and animal studies suggests that bacteria have an instrumental role in its pathogenesis. Comparison of the intestinal microbiota of patients with Crohn's disease to that of healthy controls has revealed compositional changes. In most studies these changes are characterized by an increase in the abundance of Bacteroidetes and Proteobacteria and a decrease in that of Firmicutes. In addition, a number of specific mucosa-associated bacteria have been postulated to have a role in Crohn's disease, including Mycobacterium avium subspecies paratuberculosis, adherent and invasive Escherichia coli, C ylobacter and Helicobacter species. The association between mutations in pattern-recognition receptors (Toll-like receptors and Nod-like receptors) and autophagy proteins and Crohn's disease provides further evidence to suggest that defective sensing and killing of bacteria may drive the onset of disease. In this Review, we present recent advances in understanding the role of bacteria and the contribution of pattern-recognition receptors and autophagy in the pathogenesis of Crohn's disease.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.CELREP.2018.10.103
Abstract: Intrinsic apoptosis resulting from BAX/BAK-mediated mitochondrial membrane damage is regarded as immunologically silent. We show here that in macrophages, BAX/BAK activation results in inhibitor of apoptosis (IAP) protein degradation to promote caspase-8-mediated activation of IL-1β. Furthermore, BAX/BAK signaling induces a parallel pathway to NLRP3 inflammasome-mediated caspase-1-dependent IL-1β maturation that requires potassium efflux. Remarkably, following BAX/BAK activation, the apoptotic executioner caspases, caspase-3 and -7, act upstream of both caspase-8 and NLRP3-induced IL-1β maturation and secretion. Conversely, the pyroptotic cell death effectors gasdermin D and gasdermin E are not essential for BAX/BAK-induced IL-1β release. These findings highlight that innate immune cells undergoing BAX/BAK-mediated apoptosis have the capacity to generate pro-inflammatory signals and provide an explanation as to why IL-1β activation is often associated with cellular stress, such as during chemotherapy.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Informa UK Limited
Date: 07-11-2016
Publisher: Wiley
Date: 28-12-2015
Publisher: Springer Science and Business Media LLC
Date: 27-03-2017
DOI: 10.1038/SREP45126
Abstract: Caspase-1, also known as interleukin-1β (IL-1β)-converting enzyme (ICE), regulates antimicrobial host defense, tissue repair, tumorigenesis, metabolism and membrane biogenesis. On activation within an inflammasome complex, caspase-1 induces pyroptosis and converts pro-IL-1β and pro-IL-18 into their biologically active forms. “ICE −/− ” or “ Casp1 −/− ” mice generated using 129 embryonic stem cells carry a 129-associated inactivating passenger mutation on the caspase-11 locus, essentially making them deficient in both caspase-1 and caspase-11. The overlapping and unique functions of caspase-1 and caspase-11 are difficult to unravel without additional genetic tools. Here, we generated caspase-1–deficient mouse ( Casp1 Null ) on the C57BL/6 J background that expressed caspase-11. Casp1 Null cells did not release IL-1β and IL-18 in response to NLRC4 activators Salmonella Typhimurium and flagellin, canonical or non-canonical NLRP3 activators LPS and ATP, Escherichia coli, Citrobacter rodentium and transfection of LPS, AIM2 activators Francisella novicida , mouse cytomegalovirus and DNA, and the infectious agents Listeria monocytogenes and Aspergillus fumigatus . We further demonstrated that caspase-1 and caspase-11 differentially contributed to the host defense against A. fumigatus infection and to endotoxemia.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2018
Publisher: American Society for Microbiology
Date: 15-05-2010
DOI: 10.1128/AEM.02551-09
Abstract: The C ylobacter genus consists of a number of important human and animal pathogens. Although the 16S rRNA gene has been used extensively for detection and identification of C ylobacter species, there is currently limited information on the 23S rRNA gene and the internal transcribed spacer (ITS) region that lies between the 16S and 23S rRNA genes. We examined the potential of the 23S rRNA gene and the ITS region to be used in species differentiation and delineation of systematic relationships for 30 taxa within the C ylobacter genus. The ITS region produced the highest mean pairwise percentage difference (35.94%) compared to the 16S (5.34%) and 23S (7.29%) rRNA genes. The discriminatory power for each region was further validated using Simpson's index of ersity ( D value). The D values were 0.968, 0.995, and 0.766 for the ITS region and the 23S and 16S rRNA genes, respectively. A closer examination of the ITS region revealed that C ylobacter concisus , C ylobacter showae , and C ylobacter fetus subsp. fetus harbored tRNA configurations not previously reported for other members of the C ylobacter genus. We also observed the presence of strain-dependent intervening sequences in the 23S rRNA genes. Neighbor-joining trees using the ITS region revealed that C ylobacter jejuni and C ylobacter coli strains clustered in subgroups, which was not observed in trees derived from the 16S or 23S rRNA gene. Of the three regions examined, the ITS region is by far the most cost-effective region for the differentiation and delineation of systematic relationships within the C ylobacter genus.
Publisher: Springer Science and Business Media LLC
Date: 10-12-2018
Publisher: Springer Science and Business Media LLC
Date: 10-02-2020
DOI: 10.1038/S41598-020-58849-Z
Abstract: Activation of the inflammasome is involved in the progression of retinal degenerative diseases, in particular, in the pathogenesis of Age-Related Macular Degeneration (AMD), with NLRP3 activation the focus of many investigations. In this study, we used genetic and pharmacological approaches to explore the role of the inflammasome in a mouse model of retinal degeneration. We identify that Casp1/11 −/− mice have better-preserved retinal function, reduced inflammation and increased photoreceptor survivability. While Nlrp3 − / − mice display some level of preservation of retinal function compared to controls, pharmacological inhibition of NLRP3 did not protect against photoreceptor cell death. Further, Aim2 −/− , Nlrc4 −/− , Asc −/− , and Casp11 −/− mice show no substantial retinal protection. We propose that CASP-1-associated photoreceptor cell death occurs largely independently of NLRP3 and other established inflammasome sensor proteins, or that inhibition of a single sensor is not sufficient to repress the inflammatory cascade. Therapeutic targeting of CASP-1 may offer a more promising avenue to delay the progression of retinal degenerations.
Publisher: Springer Science and Business Media LLC
Date: 05-2011
Publisher: Proceedings of the National Academy of Sciences
Date: 06-05-2014
Abstract: The nucleotide-binding oligomerization domain-like receptor (NLR) family members, NLRC4 and NLRP3, activate the inflammasome to provide host defenses against infection. The precise molecular constituents of an inflammasome are unknown however, it is believed that receptor-specific complexes containing apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) and caspase-1 are formed. Here, we used confocal and superresolution microscopy to show that in macrophages infected with Salmonella Typhimurium, a pathogen that activates two distinct NLRs, ASC forms an outer ring-like structure that comprises NLRC4, NLRP3, caspase-1, caspase-8, and pro–IL-1β within the same macromolecular complex. These results suggest that the inflammasome is a highly dynamic macromolecular protein complex capable of recruiting different NLRs and effectors to coordinate inflammasome responses to infection.
Publisher: Springer Science and Business Media LLC
Date: 20-09-2022
Publisher: Springer Science and Business Media LLC
Date: 22-07-2020
Publisher: Wiley
Date: 30-04-2017
DOI: 10.1111/IMR.12534
Publisher: Springer Science and Business Media LLC
Date: 29-07-2022
DOI: 10.1038/S41467-022-32127-0
Abstract: Inflammasomes are cytosolic signaling complexes capable of sensing microbial ligands to trigger inflammation and cell death responses. Here, we show that guanylate-binding proteins (GBPs) mediate pathogen-selective inflammasome activation. We show that mouse GBP1 and GBP3 are specifically required for inflammasome activation during infection with the cytosolic bacterium Francisella novicida . We show that the selectivity of mouse GBP1 and GBP3 derives from a region within the N-terminal domain containing charged and hydrophobic amino acids, which binds to and facilitates direct killing of F. novicida and Neisseria meningitidis , but not other bacteria or mammalian cells. This pathogen-selective recognition by this region of mouse GBP1 and GBP3 leads to pathogen membrane rupture and release of intracellular content for inflammasome sensing. Our results imply that GBPs discriminate between pathogens, confer activation of innate immunity, and provide a host-inspired roadmap for the design of synthetic antimicrobial peptides that may be of use against emerging and re-emerging pathogens.
Publisher: Wiley
Date: 08-2008
DOI: 10.1111/J.1523-5378.2008.00607.X
Abstract: Although there is compelling evidence to support the role of bacteria in Crohn's disease (CD), there is currently no solid evidence to support the role of any one specific bacterial causative agent. Recent studies have suggested that members of the Helicobacteraceae may play a role in the development of CD. The aim of this study was to further investigate the presence of members of the Helicobacteraceae in children with and without CD. Fecal specimens from 29 children with CD, 11 healthy, normal controls, and 26 symptomatic controls with non-inflammatory bowel disease (IBD) pathology were obtained for DNA extraction and subjected to Helicobacteraceae-specific polymerase chain reaction (PCR). All PCR-positive s les were sequenced. The association between the presence of members of the Helicobacteraceae and each study group was statistically analysed using the Fisher's exact test. Based on Helicobacteraceae-specific PCR analysis, 59% (17 of 29) of the children with CD were positive, which was significantly higher than that in asymptomatic healthy children [9% (1 of 11) p = .01] and that in symptomatic children with non-IBD pathology [0% (0/26) p < .0001]. Sequencing of the 16S rRNA gene of positive s les revealed the presence of both enterohepatic Helicobacter species and Helicobacter pylori in fecal specimens. For the first time, enterohepatic and gastric Helicobacter species have been identified in fecal specimens from children diagnosed with CD using PCR. Our data suggest that Helicobacter species may have a pathogenic role in the development of CD in a considerable proportion of children.
Publisher: Wiley
Date: 16-04-2015
DOI: 10.1111/IMR.12296
Publisher: Springer Science and Business Media LLC
Date: 28-10-2019
Publisher: Cold Spring Harbor Laboratory
Date: 25-10-2022
DOI: 10.1101/2022.10.24.513490
Abstract: Multidrug resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host. Pattern-recognition receptors sense microbes, and activate the inflammasome pathway, leading to pro-inflammatory cytokine production and programmed cell death. Here, we found that MDR A. baumannii activate the NLRP3 inflammasome complex predominantly via the non-canonical caspase-11-dependent pathway. We show that caspase-11-deficient mice are protected from a virulent MDR A. baumannii strain by maintaining a balance between protective and deleterious inflammation via IL-1. Caspase-11-deficient mice also compromise between effector cell recruitment, phagocytosis, and programmed cell death in the lung during infection. Importantly, we found that cytosolic immunity - mediated by guanylate-binding protein 1 (GBP1) and type I interferon signalling - orchestrates caspase-11-dependent inflammasome activation. This exerts a bactericidal activity against carbapenem- and colistin-resistant, lipooligosaccharide (LOS)- deficient bacteria. Together, our results suggest that developing therapeutic strategies targeting GBP1 might pave the way as a host-directed therapy to overcome multidrug resistance in A. baumannii infection.
Publisher: Springer Science and Business Media LLC
Date: 16-03-2015
DOI: 10.1038/NI.3118
Publisher: American Society for Microbiology
Date: 07-2015
DOI: 10.1128/CMR.00006-15
Abstract: C ylobacter jejuni infection is one of the most widespread infectious diseases of the last century. The incidence and prevalence of c ylobacteriosis have increased in both developed and developing countries over the last 10 years. The dramatic increase in North America, Europe, and Australia is alarming, and data from parts of Africa, Asia, and the Middle East indicate that c ylobacteriosis is endemic in these areas, especially in children. In addition to C. jejuni , there is increasing recognition of the clinical importance of emerging C ylobacter species, including C ylobacter concisus and C ylobacter ureolyticus . Poultry is a major reservoir and source of transmission of c ylobacteriosis to humans. Other risk factors include consumption of animal products and water, contact with animals, and international travel. Strategic implementation of multifaceted biocontrol measures to reduce the transmission of this group of pathogens is paramount for public health. Overall, c ylobacteriosis is still one of the most important infectious diseases that is likely to challenge global health in the years to come. This review provides a comprehensive overview of the global epidemiology, transmission, and clinical relevance of C ylobacter infection.
Publisher: American Association for Cancer Research (AACR)
Date: 31-01-2017
DOI: 10.1158/2326-6066.CIR-16-0269
Abstract: Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat–containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota. Activation of the inflammasome and IL18 signaling pathways is largely protective in colitis-associated colorectal cancer, whereas excessive inflammation driven by the inflammasome or the IL1 signaling pathways promotes breast cancer, fibrosarcoma, gastric carcinoma, and lung metastasis in a context-dependent manner. The clinical relevance of inflammasomes in multiple forms of cancer highlights their therapeutic promise as molecular targets. In this review, we explore the crossroads between inflammasomes and the development of various tumors and discuss possible therapeutic values in targeting the inflammasome for the prevention and treatment of cancer. Cancer Immunol Res 5(2) 94–99. ©2017 AACR.
Publisher: Public Library of Science (PLoS)
Date: 11-2022
DOI: 10.1371/JOURNAL.PONE.0277019
Abstract: Acinetobacter baumannii is an emerging nosocomial, opportunistic pathogen with growing clinical significance globally. A . baumannii has an exceptional ability to rapidly develop drug resistance. It is frequently responsible for ventilator-associated pneumonia in clinical settings and inflammation resulting in severe sepsis. The inflammatory response is mediated by host pattern-recognition receptors and the inflammasomes. Inflammasome activation triggers inflammatory responses, including the secretion of the pro-inflammatory cytokines IL-1β and IL-18, the recruitment of innate immune effectors against A . baumannii infection, and the induction programmed cell death by pyroptosis. An important knowledge gap is how variation among clinical isolates affects the host’s innate response and activation of the inflammasome during A . baumannii infection. In this study, we compared nine A . baumannii strains, including clinical locally-acquired isolates, in their ability to induce activation of the inflammasome and programmed cell death in primary macrophages, epithelial lung cell line and mice. We found a variation in survival outcomes of mice and bacterial dissemination in organs among three commercially available A . baumannii strains, likely due to the differences in virulence between strains. Interestingly, we found variability among A . baumannii strains in activation of the NLRP3 inflammasome, non-canonical Caspase-11 pathway, plasmatic secretion of the pro-inflammatory cytokine IL-1β and programmed cell death. Our study highlights the importance of utilising multiple bacterial strains and clinical isolates with different virulence to investigate the innate immune response to A . baumannii infection.
Publisher: The American Association of Immunologists
Date: 15-11-2014
Abstract: Stimulator of IFN genes (STING) is a cytoplasmic innate immune sensor for cyclic dinucleotides that also serves a dual role as an adaptor molecule for a number of intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and autoimmune diseases, its physiological role in cancer is unknown. In this study, we show that STING-deficient mice are highly susceptible to colitis-associated colorectal cancer. Colons of STING-deficient mice exhibit significant intestinal damage and overt proliferation during early stages of tumorigenesis. Moreover, STING-deficient mice fail to restrict activation of the NF-κB– and STAT3-signaling pathways, which leads to increased levels of the proinflammatory cytokines IL-6 and KC. Therefore, our results identified an unexpected and important role for STING in mediating protection against colorectal tumorigenesis.
Publisher: Life Science Alliance, LLC
Date: 21-03-2023
Abstract: Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety of PVP-I remains controversial. Its extended use in the current SARS-CoV-2 virus pandemic urges the need to clarify safety features of PVP-I on a cellular level. Our investigation in epithelial, mesothelial, endothelial, and innate immune cells revealed that the toxicity of PVP-I is caused by diatomic iodine (I 2 ), which is rapidly released from PVP-I to fuel organic halogenation with fast first-order kinetics. Eukaryotic toxicity manifests at below clinically used concentrations with a threshold of 0.1% PVP-I (wt/vol), equalling 1 mM of total available I 2 . Above this threshold, membrane disruption, loss of mitochondrial membrane potential, and abolition of oxidative phosphorylation induce a rapid form of cell death we propose to term iodoptosis. Furthermore, PVP-I attacks lipid rafts, leading to the failure of tight junctions and thereby compromising the barrier functions of surface-lining cells. Thus, the therapeutic window of PVP-I is considerably narrower than commonly believed. Our findings urge the reappraisal of PVP-I in clinical practice to avert unwarranted toxicity whilst safeguarding its benefits.
Publisher: Wiley
Date: 27-10-2016
DOI: 10.1111/EVO.13088
Abstract: Although sexual ornamentation mediates reproductive isolation, comparative evidence does not support the hypothesis that stronger sexual selection promotes speciation. Prior analyses have neglected the possibility that decreases in ornamentation may also promote speciation, such that both increases and decreases in the strength of sexual selection and associated changes in ornamentation promote speciation. To test this hypothesis, we studied color ornamentation in one of the largest and fastest avian radiations, the estrildid finches. We show that more ornamented lineages do not speciate more, even though they tend to have faster rates of ornamental evolution, whereas changes in ornamentation (i.e., increases or decreases) are associated with speciation. This indicates that ergence in sexually selected ornamentation, rather than stronger sexual selection, promotes or is otherwise associated with speciation. We also show that gregariousness and investment in reproduction are related to the elaboration of some ornamental traits, suggesting ecological influences on speciation mediated by ornamentation. We conclude that past work focusing specifically on the strength of sexual selection may have greatly underestimated the importance of sexual ornamentation for speciation.
Publisher: Springer Science and Business Media LLC
Date: 06-02-2020
DOI: 10.1038/S41467-020-14534-3
Abstract: Inflammasomes are important for host defence against pathogens and homeostasis with commensal microbes. Here, we show non-haemolytic enterotoxin (NHE) from the neglected human foodborne pathogen Bacillus cereus is an activator of the NLRP3 inflammasome and pyroptosis. NHE is a non-redundant toxin to haemolysin BL (HBL) despite having a similar mechanism of action. Via a putative transmembrane region, subunit C of NHE initiates binding to the plasma membrane, leading to the recruitment of subunit B and subunit A, thus forming a tripartite lytic pore that is permissive to efflux of potassium. NHE mediates killing of cells from multiple lineages and hosts, highlighting a versatile functional repertoire in different host species. These data indicate that NHE and HBL operate synergistically to induce inflammation and show that multiple virulence factors from the same pathogen with conserved function and mechanism of action can be exploited for sensing by a single inflammasome.
Publisher: Proceedings of the National Academy of Sciences
Date: 24-11-2014
Abstract: Infectious diseases are responsible for one-third of all mortality worldwide. Innate immunity is critical for mounting host defenses that eliminate pathogens. Salmonella is a global food-borne pathogen that infects and replicates within macrophages. How inflammasomes—multimeric protein complexes that provide innate immune protection—function to restrict bacterial burden in macrophages remains unknown. We show that actin polymerization is critical for NLRC4 inflammasome activation in response to Salmonella infection. NLRC4 activation in Salmonella -infected cells prevents further uptake of bacteria by inducing cellular stiffness and antimicrobial responses, which prevent bacterial dissemination in the host. These results demonstrate a critical link between innate immunity and the actin cytoskeleton in the cellular defense against Salmonella infection.
Publisher: Wiley
Date: 29-07-2020
DOI: 10.1111/IMR.12906
Publisher: Oxford University Press (OUP)
Date: 29-12-2017
Abstract: The inflammasome is a macromolecular protein complex that mediates proteolytic cleavage of pro-IL-1β and -IL-18 and induces cell death in the form of pyroptosis. Certain nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), or tripartite motif (TRIM) family receptors trigger the assembly of an inflammasome in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Recent studies have revealed a multitude of host components and signals that are essential for controlling canonical and noncanonical inflammasome activation and pyroptosis. These include pore-forming gasdermin proteins, the never in mitosis A-related kinase 7 (NEK7), IFN-inducible proteins (IFIs), reactive oxygen species (ROS), autophagy, potassium efflux, mitochondrial perturbations, and microbial metabolites. Here, we provide a comprehensive overview of the molecular and signaling mechanisms that provide stringent regulation over the activation and effector functions of the inflammasome.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.TCB.2021.06.010
Abstract: Organelles are critical structures in mediating the assembly and activation of inflammasomes in mammalian cells, resulting in inflammation and cell death. Assembly of inflammasomes can occur at the mitochondria, endoplasmic reticulum, nucleus, trans-Golgi network, or pathogen surface, facilitated by the overarching architecture of the cytoskeleton. NLRP3 and Pyrin inflammasome sensors may form smaller speckles and converge on a single larger speck at the microtubule-organizing center (MTOC). This signaling hub activates multiple mammalian inflammatory and apoptotic caspases, cytokine substrates, the pore-forming protein gasdermin D, and the plasma membrane rupture protein ninjurin-1 (NINJ1), allowing pyroptosis, cellular disintegration, and inflammation to ensue. In this review, we highlight the role of mammalian cell types and organellar architectures in executing inflammasome responses.
Publisher: EMBO
Date: 19-04-2023
Abstract: Inflammasome signaling is a central pillar of innate immunity triggering inflammation and cell death in response to microbes and danger signals. Here, we show that two virulence factors from the human bacterial pathogen Clostridium perfringens are nonredundant activators of the NLRP3 inflammasome in mice and humans. C. perfringens lecithinase (also known as phospolipase C) and C. perfringens perfringolysin O induce distinct mechanisms of activation. Lecithinase enters LAMP1 + vesicular structures and induces lysosomal membrane destabilization. Furthermore, lecithinase induces the release of the inflammasome‐dependent cytokines IL‐1β and IL‐18, and the induction of cell death independently of the pore‐forming proteins gasdermin D, MLKL and the cell death effector protein ninjurin‐1 or NINJ1. We also show that lecithinase triggers inflammation via the NLRP3 inflammasome in vivo and that pharmacological blockade of NLRP3 using MCC950 partially prevents lecithinase‐induced lethality. Together, these findings reveal that lecithinase activates an alternative pathway to induce inflammation during C. perfringens infection and that this mode of action can be similarly exploited for sensing by a single inflammasome.
Publisher: American Society for Microbiology
Date: 02-2015
DOI: 10.1128/IAI.03012-14
Abstract: Pathogenic species within the genus C ylobacter are responsible for a considerable burden on global health. C ylobacter concisus is an emergent pathogen that plays a role in acute and chronic gastrointestinal disease. Despite ongoing research on C ylobacter virulence mechanisms, little is known regarding the immunological profile of the host response to C ylobacter infection. In this study, we describe a comprehensive global profile of innate immune responses to C. concisus infection in differentiated THP-1 macrophages infected with an adherent and invasive strain of C. concisus . Using RNA sequencing (RNA-seq), quantitative PCR (qPCR), mass spectrometry, and confocal microscopy, we observed differential expression of pattern recognition receptors and robust upregulation of DNA- and RNA-sensing molecules. In particular, we observed IFI16 inflammasome assembly in C. concisus -infected macrophages. Global profiling of the transcriptome revealed the significant regulation of a total of 8,343 transcripts upon infection with C. concisus , which included the activation of key inflammatory pathways involving CREB1, NF-κB, STAT, and interferon regulatory factor signaling. Thirteen microRNAs and 333 noncoding RNAs were significantly regulated upon infection, including MIR221, which has been associated with colorectal carcinogenesis. This study represents a major advance in our understanding of host recognition and innate immune responses to infection by C. concisus .
Publisher: American Geophysical Union (AGU)
Date: 17-06-2015
DOI: 10.1002/2015GL064519
Publisher: Rockefeller University Press
Date: 22-08-2016
DOI: 10.1084/JEM.20151938
Abstract: Lysosomal cathepsins regulate an exquisite range of biological functions, and their deregulation is associated with inflammatory, metabolic, and degenerative diseases in humans. In this study, we identified a key cell-intrinsic role for cathepsin B as a negative feedback regulator of lysosomal biogenesis and autophagy. Mice and macrophages lacking cathepsin B activity had increased resistance to the cytosolic bacterial pathogen Francisella novicida. Genetic deletion or pharmacological inhibition of cathepsin B down-regulated mechanistic target of rapamycin activity and prevented cleavage of the lysosomal calcium channel TRPML1. These events drove transcription of lysosomal and autophagy genes via transcription factor EB, which increased lysosomal biogenesis and activation of autophagy initiation kinase ULK1 for clearance of the bacteria. Our results identified a fundamental biological function of cathepsin B in providing a checkpoint for homeostatic maintenance of lysosome populations and basic recycling functions in the cell.
Publisher: Springer Science and Business Media LLC
Date: 19-08-2021
DOI: 10.1186/S13073-021-00951-6
Abstract: The enrichment of Gram-negative bacteria of oral origin in the esophageal microbiome has been associated with the development of metaplasia. However, to date, no study has comprehensively assessed the relationships between the esophageal microbiome and the host. Here, we examine the esophageal microenvironment in gastro-esophageal reflux disease and metaplasia using multi-omics strategies targeting the microbiome and host transcriptome, followed by targeted culture, comparative genomics, and host-microbial interaction studies of bacterial signatures of interest. Profiling of the host transcriptome from esophageal mucosal biopsies revealed profound changes during metaplasia. Importantly, five biomarkers showed consistent longitudinal changes with disease progression from reflux disease to metaplasia. We showed for the first time that the esophageal microbiome is distinct from the salivary microbiome and the enrichment of C ylobacter species as a consistent signature in disease across two independent cohorts. Shape fitting and matrix correlation identified associations between the microbiome and host transcriptome profiles, with a novel co-exclusion relationship found between C ylobacter and napsin B aspartic peptidase. Targeted culture of C ylobacter species from the same cohort revealed a subset of isolates to have a higher capacity to survive within primary human macrophages. Comparative genomic analyses showed these isolates could be differentiated by specific genomic features, one of which was validated to be associated with intracellular fitness. Screening for these C ylobacter strain-specific signatures in shotgun metagenomics data from another cohort showed an increase in prevalence with disease progression. Comparative transcriptomic analyses of primary esophageal epithelial cells exposed to the C ylobacter isolates revealed expression changes within those infected with strains with high intracellular fitness that could explain the increased likelihood of disease progression. We provide a comprehensive assessment of the esophageal microenvironment, identifying bacterial strain-specific signatures with high relevance to progression of metaplasia.
Publisher: Springer Science and Business Media LLC
Date: 10-09-2020
Publisher: Elsevier BV
Date: 07-2015
Publisher: American Chemical Society (ACS)
Date: 16-05-2022
DOI: 10.1021/ACSBIOMATERIALS.2C00099
Abstract: Device-associated infections remain a clinical challenge. The common strategies to prevent bacterial infection are either toxic to healthy mammalian cells and tissue or involve high doses of antibiotics that can prompt long-term negative consequences. An antibiotic-free coating strategy to suppress bacterial growth is presented herein, which concurrently promotes bone cell growth and moderates the dissolution kinetics of resorbable magnesium (Mg) biomaterials. Pure Mg as a model biodegradable material was coated with gallium-doped strontium-phosphate through a chemical conversion process. Gallium was distributed in a gradual manner throughout the strontium-phosphate coating, with a compact structure and a gallium-rich surface. It was demonstrated that the coating protected the underlying Mg parts from significant degradation in minimal essential media at physiological conditions over 9 days. In terms of bacteria culture, the liberated gallium ions from the coatings upon Mg specimens, even though in minute quantities, inhibited the growth of Gram-positive
Publisher: Integrated Ocean Drilling Program
Date: 08-01-2016
Publisher: Wiley
Date: 06-08-2012
Abstract: Infection of cells by pathogens leads to both biochemical and structural modifications of the host cell. To study the structural modifications in a label-free manner, we use digital holographic microscopy, DHM, to obtain the integral refractive index distribution of cells. Primary murine bone marrow derived macrophages (BMDM) infected with Salmonella enterica serovar Typhimurium, undergo highly significant reduction in refractive index, RI, compared to uninfected cells. Infected BMDM cells from genetically modified mice lacking an inflammatory protein that causes cell death, caspase 1, also exhibit similar decrease in RI. These data suggest that any reduction in RI of Salmonella-infected BMDMs is pathogen induced and independent of caspase 1-induced inflammation or cell death. This finding suggests DHM may be useful for general real time monitoring of host cell interactions with infectious pathogens.
Publisher: American Society for Microbiology
Date: 12-2018
Abstract: Infection is a dynamic biological process underpinned by a complex interplay between the pathogen and the host. Microbes from all domains of life, including bacteria, viruses, fungi, and protozoan parasites, have the capacity to cause infection.
Publisher: Frontiers Media SA
Date: 16-07-2019
Publisher: Springer Science and Business Media LLC
Date: 30-03-2022
DOI: 10.1038/S41568-022-00462-5
Abstract: The immune system plays a critical role in shaping all facets of cancer, from the early initiation stage through to metastatic disease and resistance to therapy. Our understanding of the importance of the adaptive arm of the immune system in antitumour immunity has led to the implementation of immunotherapy with immune checkpoint inhibitors in numerous cancers, albeit with differing efficacy. By contrast, the clinical utility of innate immunity in cancer has not been exploited, despite dysregulated innate immunity being a feature of at least one-third of all cancers associated with tumour-promoting chronic inflammation. The past two decades have seen innate immune pattern recognition receptors (PRRs) emerge as critical regulators of the immune response to microbial infection and host tissue damage. More recently, it has become apparent that in many cancer types, PRRs play a central role in modulating a vast array of tumour-inhibiting and tumour-promoting cellular responses both in immune cells within the tumour microenvironment and directly in cancer cells. Herein, we provide a comprehensive overview of the fast-evolving field of PRRs in cancer, and discuss the potential to target PRRs for drug development and biomarker discovery in a wide range of oncology settings.
Publisher: Springer Science and Business Media LLC
Date: 13-06-2016
DOI: 10.1038/SREP27814
Abstract: Food poisoning is one of the leading causes of morbidity and mortality in the world. Citrobacter rodentium is an enteric pathogen which attaches itself to enterocytes and induces attachment and effacing (A/E) lesions. The ability of the bacterium to cause infection requires subversion of the host actin cytoskeleton. Rac-dependent actin polymerization is activated by a guanine nucleotide exchange factor known as Dedicator of cytokinesis 2 (DOCK2). However, the role of DOCK2 in infectious disease is largely unexplored. Here, we found that mice lacking DOCK2 were susceptible to C. rodentium infection. These mice harbored increased levels of C. rodentium bacteria, showed more pronounced weight loss and inflammation-associated pathology, and were prone to bacterial dissemination to the systemic organs compared with wild-type mice. We found that mice lacking DOCK2 were more susceptible to C. rodentium attachment to intestinal epithelial cells. Therefore, our results underscored an important role of DOCK2 for gastrointestinal immunity to C. rodentium infection.
Publisher: Springer Science and Business Media LLC
Date: 14-12-2015
DOI: 10.1038/NRI.2015.7
Publisher: Wiley
Date: 10-02-2010
DOI: 10.1111/J.1742-4658.2010.07587.X
Abstract: A higher prevalence of C ylobacter concisus and higher levels of IgG antibodies specific to C. concisus in Crohn's disease patients than in controls were recently detected. In this study, 1D and 2D gel electrophoresis coupled with LTQ FT-MS and QStar tandem MS, respectively, were performed to characterize the secretome of a C. concisus strain isolated from a Crohn's disease patient. Two hundred and one secreted proteins were identified, of which 86 were bioinformatically predicted to be secreted. Searches were performed on the genome of C. concisus strain 13826, and 25 genes that have been associated with virulence or colonization in other organisms were identified. The zonula occludens toxin was found only in C. concisus among the C ylobacterales, although expanded searches revealed that this protein was present in two epsilon-proteobacterial species from extreme marine environments. Alignments and structural threading indicated that this toxin shared features with that of other virulent pathogens, including Neisseria meningitidis and Vibrio cholerae. Further comparative analyses identified several associations between the secretome of C. consisus and putative virulence factors of this bacterium. This study has identified several factors putatively associated with disease outcome, suggesting that C. concisus is a pathogen of the gastrointestinal tract.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JMB.2018.07.002
Abstract: The Gasdermin (GSDM) family consists of Gasdermin A (GSDMA), Gasdermin B (GSDMB), Gasdermin C (GSDMC), Gasdermin D (GSDMD), Gasdermin E (GSDME) and Pejvakin (PJVK). GSDMD is activated by inflammasome-associated inflammatory caspases. Cleavage of GSDMD by human or mouse caspase-1, human caspase-4, human caspase-5, and mouse caspase-11 liberates the N-terminal effector domain from the C-terminal inhibitory domain. The N-terminal domain oligomerizes in the cell membrane and forms a pore of 10-16 nm in diameter, through which substrates of a smaller diameter, such as interleukin-1β and interleukin-18, are secreted. The increasing abundance of membrane pores ultimately leads to membrane rupture and pyroptosis, releasing the entire cellular content. Other than GSDMD, the N-terminal domain of all GSDMs, with the exception of PJVK, have the ability to form pores. There is evidence to suggest that GSDMB and GSDME are cleaved by apoptotic caspases. Here, we review the mechanistic functions of GSDM proteins with respect to their expression and signaling profile in the cell, with more focused discussions on inflammasome activation and cell death.
Publisher: Elsevier BV
Date: 03-2015
Publisher: Oxford University Press (OUP)
Date: 11-2014
Publisher: Elsevier BV
Date: 11-2019
Abstract: The inflammasome is a cytosolic immune signaling complex that induces inflammation and pyroptosis. Inflammasome complexes respond to a variety of pathogens, as well as danger or homeostasis-altering signals they can play critical roles in the development of autoinflammatory conditions and cancer. Studies have now provided additional insights into the activation mechanisms and regulation of established inflammasome complexes, including NLRP1b, NLRP3, NOD-like receptor family apoptosis inhibitory protein (NAIP)-NLRC4, absent in melanoma (AIM)2, caspase-11, and pyrin. New activators and regulators of emerging NLRP6 and NLRP9b inflammasome complexes have also been described. We highlight the latest progress in our understanding of the molecular mechanisms governing inflammasome activation and pyroptosis, including the discovery of the pore-forming protein gasdermin D (GSDMD). We also discuss the importance of inflammasome activators and regulators in health and disease.
Publisher: Springer Science and Business Media LLC
Date: 08-2011
DOI: 10.1038/476399D
Publisher: Oxford University Press (OUP)
Date: 14-07-2016
Abstract: Guanylate-binding proteins (GBPs) are essential components of cell-autonomous immunity. In response to IFN signaling, GBPs are expressed in the cytoplasm of immune and nonimmune cells, where they unleash their antimicrobial activity toward intracellular bacteria, viruses, and parasites. Recent studies have revealed that GBPs are essential for mediating activation of the caspase-1 inflammasome in response to the gram-negative bacteria Salmonella enterica serovar Typhimurium, Francisella novicida, Chlamydia muridarum, Chlamydia trachomatis, Legionella pneumophila, Vibrio cholerae, Enterobacter cloacae, and Citrobacter koseri. During infection with vacuolar-restricted gram-negative bacteria, GBPs disrupt the vacuolar membrane to ensure liberation of LPS for cytoplasmic detection by caspase-11 and the noncanonical NLRP3 inflammasome. In response to certain cytosolic bacteria, GBPs liberate microbial DNA for activation of the DNA-sensing AIM2 inflammasome. GBPs also promote the recruitment of antimicrobial proteins, including NADPH oxidase subunits and autophagy-associated proteins to the Mycobacterium-containing vacuole to mediate intracellular bacterial killing. Here, we provide an overview on the emerging relationship between GBPs and activation of the inflammasome in innate immunity to microbial pathogens.
Publisher: Elsevier BV
Date: 10-2016
Publisher: Oxford University Press (OUP)
Date: 06-04-2016
Publisher: Wiley
Date: 27-02-2023
DOI: 10.1111/IMCB.12627
Abstract: Many interferon (IFN)‐stimulated genes are upregulated within host cells following infection with influenza and other viruses. While the antiviral activity of some IFN‐stimulated genes, such as the IFN‐inducible GTPase myxoma resistance (Mx)1 protein 1, has been well defined, less is known regarding the antiviral activities of related IFN‐inducible GTPases of the guanylate‐binding protein (GBP) family, particularly mouse GBPs, where mouse models can be used to assess their antiviral properties in vivo . Herein, we demonstrate that mouse GBP1 (mGBP1) was upregulated in a mouse airway epithelial cell line (LA‐4 cells) following pretreatment with mouse IFNα or infection by influenza A virus (IAV). Whereas doxycycline‐inducible expression of mouse Mx1 (mMx1) in LA‐4 cells resulted in reduced susceptibility to IAV infection and reduced viral growth, inducible mGBP1 did not. Moreover, primary cells isolated from mGBP1‐deficient mice (mGBP1 −/− ) showed no difference in susceptibility to IAV and mGBP1 −/− macrophages showed no defect in IAV‐induced NLRP3 (NLR family pyrin domain containing 3) inflammasome activation. After intranasal IAV infection, mGBP1 −/− mice also showed no differences in virus replication or induction of inflammatory responses in the airways during infection. Thus, using complementary approaches such as mGBP1 overexpression, cells from mGBP1 −/− mice and intranasal infection of mGBP1 −/− we demonstrate that mGBP1 does not play a major role in modulating IAV infection in vitro or in vivo .
Publisher: Hindawi Limited
Date: 19-10-2017
DOI: 10.1111/CMI.12791
Abstract: Guanylate-binding proteins (GBPs) are a group interferon-inducible GTPases within the constellation of the dynamin GTPase superfamily. These proteins restrict the replication of intracellular pathogens in both immune and non-immune cells. GBPs and their related family members immunity-related GTPases target and lyse the membrane of the pathogen-containing vacuole, destroying the residential niche of vacuolar protozoal and bacterial pathogens. They also prevent virion infectivity and target replication complexes of ribonucleic acid viruses. The exciting concept that GBPs and immunity-related GTPases can directly target the membrane of bacteria and protozoa has emerged. Rupture and lysis of the pathogen membrane mediates liberation of concealed microbial ligands for activation of innate immune sensing pathways and the inflammasome. Further studies have demonstrated a capacity of GBPs to recruit additional antimicrobial factors, highlighting the complexity of the molecular mechanisms involved in pathogen killing. In this mini-review, we discuss recent advances describing the localisation and functions of GBPs on the host and pathogen membrane. We also highlight unresolved questions related to the regulation of GBPs in cell-autonomous immunity to intracellular pathogens.
Publisher: Proceedings of the National Academy of Sciences
Date: 17-12-2013
Abstract: Salmonella enterica serovar Typhimurium ( S. typhimurium ) is a bacterial foodborne pathogen that causes significant morbidity and mortality worldwide. Nucleotide-binding oligomerization domain–like receptor family pyrin domain containing 12 NLRP12 is a key innate immune molecule that regulates intestinal inflammation and cancer. However, its physiological function in microbial infection is not fully understood. We found that NLRP12 is a key suppressor of innate immune signaling during salmonellosis. Mice lacking NLRP12 are hyperresistant to S. typhimurium infection, and macrophages deficient in NLRP12 produce high levels of proinflammatory cytokines and other molecules contributing to pathogen clearance. Our work revealed that NLRP12-mediated d ening of host immune defenses is used by S. typhimurium to ensure its persistence and survival in host tissues. Modulation of NLRP12 activity could be useful in the prevention and treatment of salmonellosis.
Publisher: Springer Science and Business Media LLC
Date: 19-05-2015
DOI: 10.1038/NI.3174
Publisher: Elsevier BV
Date: 03-2018
Publisher: EMBO
Date: 10-02-2023
Abstract: Moraxella catarrhalis is an important human respiratory pathogen and a major causative agent of otitis media and chronic obstructive pulmonary disease. Toll‐like receptors contribute to, but cannot fully account for, the complexity of the immune response seen in M. catarrhalis infection. Using primary mouse bone marrow‐derived macrophages to examine the host response to M. catarrhalis infection, our global transcriptomic and targeted cytokine analyses revealed activation of immune signalling pathways by both membrane‐bound and cytosolic pattern‐recognition receptors. We show that M. catarrhalis and its outer membrane vesicles or lipooligosaccharide (LOS) can activate the cytosolic innate immune sensor caspase‐4/11, gasdermin‐D‐dependent pyroptosis, and the NLRP3 inflammasome in human and mouse macrophages. This pathway is initiated by type I interferon signalling and guanylate‐binding proteins (GBPs). We also show that inflammasomes and GBPs, particularly GBP2, are required for the host defence against M. catarrhalis in mice. Overall, our results reveal an essential role for the interferon‐inflammasome axis in cytosolic recognition and immunity against M. catarrhalis , providing new molecular targets that may be used to mitigate pathological inflammation triggered by this pathogen.
Publisher: Springer Science and Business Media LLC
Date: 25-10-2011
DOI: 10.1038/NRGASTRO.2011.191
Abstract: A growing number of C ylobacter species other than C. jejuni and C. coli have been recognized as emerging human and animal pathogens. Although C. jejuni continues to be the leading cause of bacterial gastroenteritis in humans worldwide, advances in molecular biology and development of innovative culture methodologies have led to the detection and isolation of a range of under-recognized and nutritionally fastidious C ylobacter spp., including C. concisus, C. upsaliensis and C. ureolyticus. These emerging C ylobacter spp. have been associated with a range of gastrointestinal diseases, particularly gastroenteritis, IBD and periodontitis. In some instances, infection of the gastrointestinal tract by these bacteria can progress to life-threatening extragastrointestinal diseases. Studies have shown that several emerging C ylobacter spp. have the ability to attach to and invade human intestinal epithelial cells and macrophages, damage intestinal barrier integrity, secrete toxins and strategically evade host immune responses. Members of the C ylobacter genus naturally colonize a wide range of hosts (including pets, farm animals and wild animals) and are frequently found in contaminated food products, which indicates that these bacteria are at risk of zoonotic transmission to humans. This Review presents the latest information on the role and clinical importance of emerging C ylobacter spp. in gastrointestinal health and disease.
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2019
End Date: 12-2022
Amount: $560,000.00
Funder: Australian Research Council
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