ORCID Profile
0000-0001-5158-7700
Current Organisations
Charles Darwin University
,
Menzies School of Health Research
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Publisher: Elsevier BV
Date: 2010
Abstract: Infection with Plasmodium parasites can cause severe disease due to a lack of protective immune responses to clear parasitemia, or to the host's inability to control excessive inflammation resulting in immunopathology. T regulatory cells (Tregs), key mediators of immune homeostasis, are increased in number and modulate disease in human and murine malaria. Several recent studies provide new insights into the mechanisms and functional consequences of Treg induction by P. falciparum. This review integrates and discusses the findings published on Tregs in human and murine malaria to date, with emphasis on Treg induction (host components, kinetics and parasite-dependence) and their erse roles (protective or pathological) during infection.
Publisher: Oxford University Press (OUP)
Date: 15-10-2018
Abstract: This study identified CD16+ DCs as the only blood DC subset distinctively activated during primary blood-stage human Plasmodium infection. As TNF/IL-10 coproducers, CD16+ DCs contribute to early inflammatory processes, yet P falciparum restimulation skewed cytokine responses further towards IL-10 production.
Publisher: Springer Science and Business Media LLC
Date: 06-2017
DOI: 10.1038/S41598-017-02096-2
Abstract: Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum- parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro . Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR 0.07). There was no upregulation of co-stimulatory molecules CD86, CD80, CD40, and reduced surface expression of HLA-DR and CD123 (IL-3R-α). pDC loss from the circulation was associated with active caspase-3, suggesting pDC apoptosis during primary infection. pDC remained responsive to TLR stimulation, producing IFN-α and upregulating HLA-DR, CD86, CD123 at peak-infection. In clinical malaria, pDC retained HLA-DR but reduced CD123 expression compared to convalescence. These data demonstrate pDC retain function during a first blood-stage P. falciparum exposure despite sub-microscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection.
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.VACCINE.2006.09.086
Abstract: DNA formulations provide the basis for safe and cost efficient vaccines. However, naked plasmid DNA is only poorly immunogenic and new effective delivery strategies are needed to enhance the potency of DNA vaccines. In this study, we present a novel approach for the delivery of DNA vaccines using inert poly-L-lysine (PLL) coated polystyrene particles, which greatly enhance DNA immunogenicity. Intradermal injection of plasmid DNA encoding for chicken egg ovalbumin (OVA) complexed with PLL-coated polystyrene nanoparticles induced high levels of CD8 T cells as well as OVA-specific antibodies in C57BL/6 mice and furthermore inhibited tumour growth after challenge with the OVA expressing EG7 tumour cell line. Importantly, vaccine efficacy depended critically on the size of the particles used as well as on the presence of the PLL linker. Our data show that PLL-coated polystyrene nanoparticles of 0.05 microm but not 0.02 microm or 1.0 microm in diameter are highly effective for the delivery of DNA vaccines.
Publisher: Wiley
Date: 30-08-0011
DOI: 10.1111/RESP.14587
Abstract: The importance of extracellular traps (ETs) in chronic respiratory conditions is increasingly recognized but their role in paediatric bronchiectasis is poorly understood. The specialized techniques currently required to study ETs preclude routine clinical use. A simple and cost‐effective ETs detection method is needed to support diagnostic applications. We aimed to determine whether ETs could be detected using light microscopy‐based assessment of Romanowsky‐stained bronchoalveolar lavage (BAL) slides from children with bronchiectasis, and whether the ETs cellular origin could be determined. Archived Romanowsky‐stained BAL slides from a cross‐sectional study of children with bronchiectasis were examined for ETs using light microscopy. The cellular origin of in idual ETs was determined based on morphology and physical contact with surrounding cell(s). ETs were observed in 78.7% (70/89) of BAL slides with neutrophil (NETs), macrophage (METs), eosinophil (EETs) and lymphocyte (LETs) ETs observed in 32.6%, 51.7%, 4.5% and 9%, respectively. ETs of indeterminate cellular origin were present in 59.6% of slides. Identifiable and indeterminate ETs were co‐detected in 43.8% of slides. BAL from children with bronchiectasis commonly contains multiple ET types that are detectable using Romanowsky‐stained slides. While specialist techniques remain necessary to determining the cellular origin of all ETs, screening of Romanowsky‐stained slides presents a cost‐effective method that is well‐suited to diagnostic settings. Our findings support further research to determine whether ETs can be used to define respiratory endotypes and to understand whether ETs‐specific therapies may be required to resolve airway inflammation among children with bronchiectasis.
Publisher: The American Association of Immunologists
Date: 15-09-2010
Abstract: The cooperative nature of tetraspanin–tetraspanin interactions in membrane organization suggests functional overlap is likely to be important in tetraspanin biology. Previous functional studies of the tetraspanins CD37 and Tssc6 in the immune system found that both CD37 and Tssc6 regulate T cell proliferative responses in vitro. CD37−/− mice also displayed a hyper-stimulatory dendritic cell phenotype and dysregulated humoral responses. In this study, we characterize “double knockout” mice (CD37−/−Tssc6−/−) generated to investigate functional overlap between these tetraspanins. Strong evidence for a cooperative role for these two proteins was identified in cellular immunity, where both in vitro T cell proliferative responses and dendritic cell stimulation capacity are significantly exaggerated in CD37−/−Tssc6−/− mice when compared with single knockout counterparts. Despite these exaggerated cellular responses in vitro, CD37−/−Tssc6−/− mice are not more susceptible to autoimmune induction. However, in vivo responses to pathogens appear poor in CD37−/−Tssc6−/− mice, which showed a reduced ability to produce influenza-specific T cells and displayed a rapid onset hyper-parasitemia when infected with Plasmodium yoelii. Therefore, in the absence of both CD37 and Tssc6, immune function is further altered when compared with CD37−/− or Tssc6−/− mice, demonstrating a complementary role for these two molecules in cellular immunity.
Publisher: Informa UK Limited
Date: 06-11-2008
DOI: 10.1517/14712590802494501
Abstract: The basis of T cell immune responses is the specific recognition of an immunogenic peptide epitope by a T cell receptor. Peptide alterations of such T cell epitopes with single or few amino acid variations can have drastic effects on the outcome of this recognition. These altered peptide ligands can act as modulators of immune responses as they are capable of downregulating or upregulating responses. We review how altered peptide ligands can have 'good' 'bad' and 'ugly' outcomes in treating diseases. Altered peptide ligands have been used as immunotherapeutics in autoimmune (and allergic) diseases, infectious diseases and cancer. In the next five years we anticipate seeing a number of altered peptide ligands in clinical trials, progressing from contradictory classifications of good, bad or ugly, to the exciting outcome of 'useful'.
Publisher: Massachusetts Medical Society
Date: 27-05-2021
DOI: 10.1056/NEJMC2023884
Publisher: Springer Science and Business Media LLC
Date: 21-06-2016
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-09-2019
Abstract: IgM is an important and long-lived component of anti-malarial immunity in humans and blocks infection of red blood cells.
Publisher: Springer Science and Business Media LLC
Date: 2014
DOI: 10.1186/CC14003
Publisher: Springer Science and Business Media LLC
Date: 06-09-2022
DOI: 10.1186/S12936-022-04268-6
Abstract: Circulating myeloid-derived-suppressor-cells (MDSC) with immunosuppressive function are increased in human experimental Plasmodium falciparum infection, but have not been studied in clinical malaria. Using flow-cytometry, circulating polymorphonuclear-MDSC were evaluated in cryopreserved s les from patients with uncomplicated Plasmodium vivax (n = 8) and uncomplicated (n = 4) and severe (n = 16) falciparum malaria from Papua, Indonesia. The absolute number of circulating polymorphonuclear-MDSC were significantly elevated in severe falciparum malaria patients compared to controls (n = 10). Polymorphonuclear-MDSC levels in uncomplicated vivax malaria were also elevated to levels comparable to that seen in severe falciparum malaria. Control of expansion of immunosuppressive MDSC may be important for development of effective immune responses in falciparum and vivax malaria.
Publisher: Elsevier BV
Date: 04-2004
Publisher: Wiley
Date: 04-01-2022
DOI: 10.1111/JACE.18300
Abstract: Engineering the optical bandgaps of classic ferroelectrics from the typical ultraviolet range down to the visible range is an emerging methodology of developing the next‐generation optoelectric and opto‐ferroelectric devices including ferroelectric solar cells, light‐driven transistors and modulators, and multi‐sensors/energy harvesters. Recently, a material interface comprised of a pseudo‐morphotropic phase boundary between the tungsten bronze and perovskite phases of the KNBNNO [(K,Na,Ba) x (Ni,Nb) y O z ] has been reported to be an effective approach for bandgap engineering while retaining excellent ferroelectricity and piezoelectricity of the perovskite‐phased KNBNNO. However, this approach requires the compositions of the materials to be determined at the synthesis stage, leaving little room for any further modification of the microstructure and functional properties at the post‐processing stage. This paper presents a post‐processing method, that is, atmospheric annealing in N 2 and O 2 , to grow the necessary tungsten bronze phase out of the perovskite phase in the KNBNNO. This method is advantageous over the previously reported because it enables to grow the tungsten bronze–perovskite interface region independent of the initial composition. The distinctive electrical properties and the giant tunability of photoconductivity of the tungsten bronze phase, the perovskite phase, and the interface are characterized in detail in this paper, supporting the exploitation of fabricating opto‐ferroelectric devices using the reported method which is compatible and comparable with some of the post‐processing methods applied in the silicon industry.
Publisher: Rockefeller University Press
Date: 08-07-2013
DOI: 10.1084/JEM.20121972
Abstract: Malaria causes significant morbidity worldwide and a vaccine is urgently required. Plasmodium infection causes considerable immune dysregulation, and elicitation of vaccine immunity remains challenging. Given the central role of dendritic cells (DCs) in initiating immunity, understanding their biology during malaria will improve vaccination outcomes. Circulating DCs are particularly important, as they shape immune responses in vivo and reflect the functional status of other subpopulations. We performed cross-sectional and longitudinal assessments of the frequency, phenotype, and function of circulating DC in 67 Papuan adults during acute uncomplicated P. falciparum, P. vivax, and convalescent P. falciparum infections. We demonstrate that malaria patients display a significant reduction in circulating DC numbers and the concurrent accumulation of immature cells. Such alteration is associated with marked levels of spontaneous apoptosis and impairment in the ability of DC to mature, capture, and present antigens to T cells. Interestingly, sustained levels of plasma IL-10 were observed in patients with acute infection and were implicated in the induction of DC apoptosis. DC apoptosis was reversed upon IL-10 blockade, and DC function recovered when IL-10 levels returned to baseline by convalescence. Our data provide key information on the mechanisms behind DC suppression during malaria and will assist in developing strategies to better harness DC’s immunotherapeutic potential.
Publisher: American Chemical Society (ACS)
Date: 07-08-2020
Publisher: American Society for Microbiology
Date: 06-2017
DOI: 10.1128/IAI.00986-16
Abstract: Plasmodium vivax malaria remains a major public health problem. The requirements for acquisition of protective immunity to the species are not clear. Dendritic cells (DC) are essential for immune cell priming but also perform immune regulatory functions, along with regulatory T cells (Treg). An important function of DC involves activation of the kynurenine pathway via indoleamine 2,3-dioxygenase (IDO). Using a controlled human experimental infection study with blood-stage P. vivax , we characterized plasmacytoid DC (pDC) and myeloid DC (mDC) subset maturation, CD4 + CD25 + CD127 lo Treg activation, and IDO activity. Blood s les were collected from six healthy adults preinoculation, at peak parasitemia (day 14 ∼31,400 parasites/ml), and 24 and 48 h after antimalarial treatment. CD1c + and CD141 + mDC and pDC numbers markedly declined at peak parasitemia, while CD16 + mDC numbers appeared less affected. HLA-DR expression was selectively reduced on CD1c + mDC, increased on CD16 + mDC, and was unaltered on pDC. Plasma IFN-γ increased significantly and was correlated with an increased kynurenine/tryptophan (KT) ratio, a measure of IDO activity. At peak parasitemia, Treg presented an activated CD4 + CD25 + CD127 lo CD45RA − phenotype and upregulated TNFR2 expression. In a mixed-effects model, the KT ratio was positively associated with an increase in activated Treg. Our data demonstrate that a primary P. vivax infection exerts immune modulatory effects by impairing HLA-DR expression on CD1c + mDC while activating CD16 + mDC. Induction of the kynurenine pathway and increased Treg activation, together with skewed mDC maturation, suggest P. vivax promotes an immunosuppressive environment, likely impairing the development of a protective host immune response.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-12-2018
DOI: 10.1161/CIRCULATIONAHA.118.033891
Abstract: Acute rheumatic fever (ARF) and rheumatic heart disease are autoimmune consequences of group A streptococcus infection and remain major causes of cardiovascular morbidity and mortality around the world. Improved treatment has been stymied by gaps in understanding key steps in the immunopathogenesis of ARF and rheumatic heart disease. This study aimed to identify (1) effector T cell cytokine(s) that might be dysregulated in the autoimmune response of patients with ARF by group A streptococcus, and (2) an immunomodulatory agent that suppresses this response and could be clinically translatable to high-risk patients with ARF. The immune response to group A streptococcus was analyzed in peripheral blood mononuclear cells from an Australian Aboriginal ARF cohort by a combination of multiplex cytokine array, flow cytometric analysis, and global gene expression analysis by RNA sequencing. The immunomodulatory drug hydroxychloroquine was tested for effects on this response. We found a dysregulated interleukin-1β-granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine axis in ARF peripheral blood mononuclear cells exposed to group A streptococcus in vitro, whereby persistent interleukin-1β production is coupled to overproduction of GM-CSF and selective expansion of CXCR3 + CCR4 − CCR6 − CD4 T cells. CXCR3 + CCR4 − CCR6 − CD4 T cells are the major source of GM-CSF in human CD4 T cells and CXCL10, a CXCR3 ligand and potent T helper 1 chemoattractant, was elevated in sera from patients with ARF. GM-CSF has recently emerged as a key T cell-derived effector cytokine in numerous autoimmune diseases, including myocarditis, and the production of CXCL10 may explain selective trafficking of these cells to the heart. We provide evidence that interleukin-1β lifies the expansion of GM-CSF-expressing CD4 T cells, which is effectively suppressed by hydroxychloroquine. RNA sequencing showed shifts in gene expression profiles and differentially expressed genes in peripheral blood mononuclear cells derived from patients at different clinical stages of ARF. Given the safety profile of hydroxychloroquine and its clinical pedigree in treating autoimmune diseases such as rheumatoid arthritis, where GM-CSF plays a pivotal role, we propose that hydroxychloroquine could be repurposed to reduce the risk of rheumatic heart disease after ARF.
Publisher: American Society for Microbiology
Date: 05-2016
DOI: 10.1128/IAI.01522-15
Abstract: Dendritic cells (DCs) are sentinels of the immune system that uniquely prime naive cells and initiate adaptive immune responses. CD1c (BDCA-1) myeloid DCs (CD1c + mDCs) highly express HLA-DR, have a broad Toll-like receptor (TLR) repertoire, and secrete immune modulatory cytokines. To better understand immune responses to malaria, CD1c + mDC maturation and cytokine production were examined in healthy volunteers before and after experimental intravenous Plasmodium falciparum infection with 150- or 1,800-parasite-infected red blood cells (pRBCs). After either dose, CD1c + mDCs significantly reduced HLA-DR expression in prepatent infections. Circulating CD1c + mDCs did not upregulate HLA-DR after pRBC or TLR ligand stimulation and exhibited reduced CD86 expression. At peak parasitemia, CD1c + mDCs produced significantly more tumor necrosis factor (TNF), whereas interleukin-12 (IL-12) production was unchanged. Interestingly, only the 1,800-pRBC dose caused a reduction in the circulating CD1c + mDC count with evidence of apoptosis. The 1,800-pRBC dose produced no change in T cell IFN-γ or IL-2 production at peak parasitemia or at 3 weeks posttreatment. Overall, CD1c + mDCs are compromised by P. falciparum exposure, with impaired HLA-DR and CD86 expression, and have an increased capacity for TNF but not IL-12 production. A first prepatent P. falciparum infection is sufficient to modulate CD1c + mDC responsiveness, likely contributing to h ered effector T cell cytokine responses and assisting parasite immune evasion.
Publisher: Oxford University Press (OUP)
Date: 19-11-2018
Abstract: Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe malaria. The role of NETs in the pathogenesis of severe malaria has not been examined. In Papua, Indonesia, we enrolled adults with symptomatic Plasmodium falciparum (n = 47 uncomplicated, n = 8 severe), Plasmodium vivax (n = 37), or Plasmodium malariae (n = 14) malaria asymptomatic P falciparum (n = 19) or P vivax (n = 21) parasitemia and healthy adults (n = 23) without parasitemia. Neutrophil activation and NETs were quantified by immunoassays and microscopy and correlated with parasite biomass and disease severity. In patients with symptomatic malaria, neutrophil activation and NET counts were increased in all 3 Plasmodium species. In falciparum malaria, neutrophil activation and NET counts positively correlated with parasite biomass (Spearman rho = 0.41, P = .005 and r2 = 0.26, P = .002, respectively) and were significantly increased in severe disease. In contrast, NETs were inversely associated with parasitemia in adults with asymptomatic P falciparum infection (r2 = 0.24, P = .031) but not asymptomatic P vivax infection. Although NETs may inhibit parasite growth in asymptomatic P falciparum infection, neutrophil activation and NET release may contribute to pathogenesis in severe falciparum malaria. Agents with potential to attenuate these processes should be evaluated.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2022
DOI: 10.1038/S41467-022-31880-6
Abstract: T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use s les from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages. We identify a dramatic re-distribution of the Tfh cell compartment with age that is independent of malaria exposure, with Th2-Tfh cells predominating in early childhood, while Th1-Tfh cell gradually increase to adult levels over the first decade of life. Functional antibody acquisition is age-dependent and hierarchical acquired based on parasite stage, with merozoite responses followed by sporozoite and gametocyte antibodies. Antibodies are boosted in children with current infection, and are higher in females. The children with the very highest antibody levels have increased Tfh cell activation and proliferation, consistent with a key role of Tfh cells in antibody development. Together, these data reveal a complex relationship between the circulating Tfh compartment, antibody development and protection from malaria.
Publisher: SAGE Publications
Date: 06-2001
Publisher: Frontiers Media SA
Date: 14-02-2017
Publisher: Elsevier BV
Date: 04-2010
Publisher: Public Library of Science (PLoS)
Date: 26-05-2021
DOI: 10.1371/JOURNAL.PMED.1003632
Abstract: A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human in iduals infected with Plasmodium vivax . The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P . vivax develops, may display high densities in the spleen, thereby providing a niche for parasite survival. We examined spleen tissue in 22 mostly untreated in iduals naturally exposed to P . vivax and Plasmodium falciparum undergoing splenectomy for any clinical indication in malaria-endemic Papua, Indonesia (2015 to 2017). Infection, parasite and immature reticulocyte density, and splenic distribution were analysed by optical microscopy, flow cytometry, and molecular assays. Nine non-endemic control spleens from in iduals undergoing spleno-pancreatectomy in France (2017 to 2020) were also examined for reticulocyte densities. There were no exclusion criteria or s le size considerations in both patient cohorts for this demanding approach. In Indonesia, 95.5% (21/22) of splenectomy patients had asymptomatic splenic Plasmodium infection (7 P . vivax , 13 P . falciparum , and 1 mixed infection). Significant splenic accumulation of immature CD71 intermediate- and high-expressing reticulocytes was seen, with concentrations 11 times greater than in peripheral blood. Accordingly, in France, reticulocyte concentrations in the splenic effluent were higher than in peripheral blood. Greater rigidity of reticulocytes in splenic than in peripheral blood, and their higher densities in splenic cords both suggest a mechanical retention process. Asexual-stage P . vivax -infected erythrocytes of all developmental stages accumulated in the spleen, with non-phagocytosed parasite densities 3,590 times (IQR: 2,600 to 4,130) higher than in circulating blood, and median total splenic parasite loads 81 (IQR: 14 to 205) times greater, accounting for 98.7% (IQR: 95.1% to 98.9%) of the estimated total-body P . vivax biomass. More reticulocytes were in contact with sinus lumen endothelial cells in P . vivax - than in P . falciparum -infected spleens. Histological analyses revealed 96% of P . vivax rings/trophozoites and 46% of schizonts colocalised with 92% of immature reticulocytes in the cords and sinus lumens of the red pulp. Larger splenic cohort studies and similar investigations in untreated symptomatic malaria are warranted. Immature CD71 + reticulocytes and splenic P . vivax- infected erythrocytes of all asexual stages accumulate in the same splenic compartments, suggesting the existence of a cryptic endosplenic lifecycle in chronic P . vivax infection. Findings provide insight into P . vivax -specific adaptions that have evolved to maximise survival and replication in the spleen.
Publisher: Oxford University Press (OUP)
Date: 28-06-2019
Abstract: Anemia is a major complication of vivax malaria. Antiphosphatidylserine (PS) antibodies generated during falciparum malaria mediate phagocytosis of uninfected red blood cells that expose PS and have been linked to late malarial anemia. However, their role in anemia from non-falciparum Plasmodium species is not known, nor their role in early anemia from falciparum malaria. We measured PS immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies in Malaysian patients with vivax, falciparum, knowlesi, and malariae malaria, and in healthy controls, and correlated antibody titres with hemoglobin. PS antibodies were also measured in volunteers experimentally infected with Plasmodium vivax and Plasmodium falciparum. PS IgM and IgG antibodies were elevated in patients with vivax, falciparum, knowlesi, and malariae malaria (P & .0001 for all comparisons with controls) and were highest in vivax malaria. In vivax and falciparum malaria, PS IgM and IgG on admission correlated inversely with admission and nadir hemoglobin, controlling for parasitemia and fever duration. PS IgM and IgG were also increased in volunteers infected with blood-stage P. vivax and P. falciparum, and were higher in P. vivax infection. PS antibodies are higher in vivax than falciparum malaria, correlate inversely with hemoglobin, and may contribute to the early loss of uninfected red blood cells found in malarial anemia from both species.
Publisher: Informa UK Limited
Date: 09-2008
DOI: 10.1586/14760584.7.7.1103
Abstract: Immunotherapy and preventative cancer vaccines offer the hope of controlling cancer in humans with few of the undesirable side effects associated with current chemotherapy-based methods. Particulate vaccines are effectively taken up by dendritic cells, inducing both T-cell and antibody responses. Virus-like particles (VLPs) have shown preventive efficacy against cervical cancer. Herein we review a range of leading particle-based vaccine approaches: VLPs, immunostimulating complexes, liposomes, synthetic nanoparticles and microparticles (both biocompatible and biodegradable, such as polylactide-co-glycolides and poly[D,L-lactic-co-glycolic] acid). Immune efficacy, regulatory and safety issues, as well the application of immunotherapeutics to immunosuppressed patients with high levels of Tregs are also discussed. We argue that developmental issues (cost and intellectual property lifespan) and the lack of reliable preclinical animal models, rather than the lack of innovative vaccine approaches, currently present a major obstacle to rapid and effective vaccine development.
Publisher: IOP Publishing
Date: 07-08-2023
Abstract: Ambient energy harvesting has great potential to contribute to sustainable development and address growing environmental challenges. Converting waste energy from energy-intensive processes and systems (e.g. combustion engines and furnaces) is crucial to reducing their environmental impact and achieving net-zero emissions. Compact energy harvesters will also be key to powering the exponentially growing smart devices ecosystem that is part of the Internet of Things, thus enabling futuristic applications that can improve our quality of life (e.g. smart homes, smart cities, smart manufacturing, and smart healthcare). To achieve these goals, innovative materials are needed to efficiently convert ambient energy into electricity through various physical mechanisms, such as the photovoltaic effect, thermoelectricity, piezoelectricity, triboelectricity, and radiofrequency wireless power transfer. By bringing together the perspectives of experts in various types of energy harvesting materials, this Roadmap provides extensive insights into recent advances and present challenges in the field. Additionally, the Roadmap analyses the key performance metrics of these technologies in relation to their ultimate energy conversion limits. Building on these insights, the Roadmap outlines promising directions for future research to fully harness the potential of energy harvesting materials for green energy anytime, anywhere.
Publisher: Elsevier BV
Date: 08-2007
Abstract: Malaria vaccines aim to induce long lasting protective immunity. Bejon and colleagues propose that levels of rapidly induced (effector memory) interleukin-2 and interferon gamma producing T-cells after vaccination with leading pre-erythrocytic stage vaccines predict the induction of resting memory responses (central memory). Herein we discuss Bejon's findings in the context of current thinking on the generation and maintenance of T cell memory, with particular emphasis on the role of cytokines.
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.YMETH.2006.05.016
Abstract: The use of particulate carriers holds great promise for the development of effective and affordable recombinant vaccines. Rational development requires a detailed understanding of particle up-take and processing mechanisms to target cellular pathways capable of stimulating the required immune responses safely. These mechanisms are in turn based on how the host has evolved to recognize and process pathogens. Pathogens, as well as particulate vaccines, come in a wide range of sizes and biochemical compositions. Some of these also provide 'danger signals' so that antigen 'senting cells (APC), usually dendritic cells (DC), acquire specific stimulatory activity. Herein, we provide an overview of the types of particles currently under investigation for the formulation of vaccines, discuss cellular uptake mechanisms (endocytosis, macropinocytosis, phagocytosis, clathrin-dependent and/or caveloae-mediated) for pathogens and particles of different sizes, as well as antigen possessing and presentation by APC in general, and DC in particular. Since particle size and composition can influence the immune response, inducing humoral and/or cellular immunity, activating CD8 T cells and/or CD4 T cells of T helper 1 and/or T helper 2 type, particle characteristics have a major impact on vaccine efficacy. Recently developed methods for the formulation of particulate vaccines are presented in this issue of Methods, showcasing a range of "cutting edge" particulate vaccines that employ particles ranging from nano to micro-sized. This special issue of Methods further addresses practical issues of production, affordability, reproducibility and stability of formulation, and also includes a discussion of the economic and regulatory challenges encountered in developing vaccines for veterinary use and for common Third World infectious diseases.
Publisher: Public Library of Science (PLoS)
Date: 24-04-2009
Publisher: Wiley
Date: 25-04-2006
Abstract: The leading blood-stage malaria vaccine candidate antigen, Plasmodium falciparum merozoite surface protein-1 (MSP-1) occurs in two major allelic types worldwide. The molecular basis promoting this stable dimorphism is unknown. In this study, we have shown that allelic altered peptide ligand (APL) T cell epitopes of MSP-1 mutually inhibited IFN-gamma secretion as well as proliferation of CD4+ T cells in 27/34 malaria exposed Gambian volunteers. Besides this inhibition of malaria-specific immunity, the same variant epitopes were also able to impair the priming of human T cells in malaria naive in iduals. Epitope variants capable of interfering with T cell priming as well as inhibiting memory T cell effector functions offer a uniquely potent combination for immune evasion. Indeed, enhanced co-habitation of parasites bearing such antagonistic allelic epitope regions was observed in a study of 321 West African children, indicating a survival advantage for parasites able to engage this inhibitory immune interference mechanism.
Publisher: Oxford University Press (OUP)
Date: 15-04-2011
Publisher: Springer Science and Business Media LLC
Date: 16-02-2021
DOI: 10.1186/S12936-021-03642-0
Abstract: Plasmodium falciparum malaria increases plasma levels of the cytokine Fms-like tyrosine kinase 3 ligand (Flt3L), a haematopoietic factor associated with dendritic cell (DC) expansion. It is unknown if the zoonotic parasite Plasmodium knowlesi impacts Flt3L or DC in human malaria. This study investigated circulating DC and Flt3L associations in adult malaria and in submicroscopic experimental infection. Plasma Flt3L concentration and blood CD141 + DC, CD1c + DC and plasmacytoid DC (pDC) numbers were assessed in (i) volunteers experimentally infected with P. falciparum and in Malaysian patients with uncomplicated (ii) P. falciparum or (iii) P. knowlesi malaria. Plasmodium knowlesi caused a decline in all circulating DC subsets in adults with malaria. Plasma Flt3L was elevated in acute P. falciparum and P. knowlesi malaria with no increase in a subclinical experimental infection. Circulating CD141 + DCs, CD1c + DCs and pDCs declined in all adults tested, for the first time extending the finding of DC subset decline in acute malaria to the zoonotic parasite P. knowlesi . In adults, submicroscopic Plasmodium infection causes no change in plasma Flt3L but does reduce circulating DCs. Plasma Flt3L concentrations increase in acute malaria, yet this increase is insufficient to restore or expand circulating CD141 + DCs, CD1c + DCs or pDCs. These data imply that haematopoietic factors, yet to be identified and not Flt3L, involved in the sensing/maintenance of circulating DC are impacted by malaria and a submicroscopic infection. The zoonotic P. knowlesi is similar to other Plasmodium spp in compromising DC in adult malaria.
Publisher: Oxford University Press (OUP)
Date: 21-05-2012
Abstract: Dendritic cells (DCs) are highly specialized antigen-presenting cells that are crucial for initiation of immune responses. During naturally acquired malaria, DC number and function is reduced. The timing of, parasitemia threshold of, and contribution of apoptosis to DC loss were prospectively evaluated in 10 men after experimental challenge with approximately 1800 Plasmodium falciparum-parasitized red blood cells (pRBCs) and after drug cure initiated at a parasite level of ≥ 1000 parasites/mL. The nadir levels of total, myeloid, and plasmacytoid DCs occurred 8 days after infection. DC loss was partially attributable to apoptosis, which was first detected on day 5 (median parasite level, 238 parasites/mL) and maximal at day 7. Remaining DCs exhibited a reduced ability to uptake particulate antigen. DC numbers recovered approximately 60 hours after antimalarial drug administration. There was no loss of DC number or function before or after drug cure in 5 men inoculated with <180 pRBCs and treated on day 6, when their parasite level was approximately 200 parasites/mL. Plasmodium causes DC loss in vivo, which is at least partially explained by apoptosis in response to blood-stage parasites. In primary infection, loss of DC number and function occurs early during the prepatent period and before or with onset of clinical symptoms. These findings may explain in part the inadequate development of immunity to blood-stage malaria infection.
Publisher: Wiley
Date: 2020
DOI: 10.1002/CTI2.1209
Publisher: Elsevier BV
Date: 11-2012
Abstract: A system for experimentally induced blood stage malaria infection (IBSM) with Plasmodium falciparum by direct intravenous inoculation of infected erythrocytes was developed at the Queensland Institute of Medical Research (QIMR) more than 15 years ago. Since that time, this system has been used in several studies to investigate the protective effect of vaccines, the clearance kinetics of parasites following drug treatment, and to improve understanding of the early events in blood stage infection. In this article, we will review the development of IBSM and the applications for which it is being employed. We will discuss the advantages and disadvantages of IBSM, and finish by describing some exciting new areas of research that have been made possible by this system.
Publisher: American Society for Microbiology
Date: 08-2015
DOI: 10.1128/IAI.00226-15
Abstract: Clinical illness with Plasmodium falciparum or Plasmodium vivax compromises the function of dendritic cells (DC) and expands regulatory T (Treg) cells. In iduals with asymptomatic parasitemia have clinical immunity, restricting parasite expansion and preventing clinical disease. The role of DC and Treg cells during asymptomatic Plasmodium infection is unclear. During a cross-sectional household survey in Papua, Indonesia, we examined the number and activation of blood plasmacytoid DC (pDC), CD141 + , and CD1c + myeloid DC (mDC) subsets and Treg cells using flow cytometry in 168 afebrile children (of whom 15 had P. falciparum and 36 had P. vivax infections) and 162 afebrile adults (of whom 20 had P. falciparum and 20 had P. vivax infections), alongside s les from 16 patients hospitalized with uncomplicated malaria. Unlike DC from malaria patients, DC from children and adults with asymptomatic, microscopy-positive P. vivax or P. falciparum infection increased or retained HLA-DR expression. Treg cells in asymptomatic adults and children exhibited reduced activation, suggesting increased immune responsiveness. The pDC and mDC subsets varied according to clinical immunity (asymptomatic or symptomatic Plasmodium infection) and, in asymptomatic infection, according to host age and parasite species. In conclusion, active control of asymptomatic infection was associated with and likely contingent upon functional DC and reduced Treg cell activation.
Publisher: American Society of Hematology
Date: 06-02-2017
DOI: 10.1182/BLOOD-2018-05-849307
Abstract: Platelets directly interact with and kill circulating Plasmodium parasites in patients with malaria to help control parasitemia. In vitro platelet antiplasmodicidal activity against P knowlesi involves platelet–cell binding and intracellular accumulation of PF4.
Publisher: Springer US
Date: 2022
DOI: 10.1007/978-1-0716-2189-9_53
Abstract: This protocol outlines a method for the timely detection of intracellular cytokines produced by activated dendritic cells (DC) in human whole blood. The quantification of cytokines is used to measure DC immune responsiveness, providing information on the breadth, strength, and DC subtypes responding spontaneously and to specific stimulation with toll-like receptor (TLR) ligands or parasite-infected erythrocytes. DC subsets, plasmacytoid DC, CD1c
Publisher: The American Association of Immunologists
Date: 08-2001
DOI: 10.4049/JIMMUNOL.167.3.1624
Abstract: Acute and chronic hyperinflammation are of major clinical concern, and many treatment strategies are therefore directed to inactivating parts of the inflammatory system. However, survival depends on responding quickly to pathogen attack, and since the adaptive immune system requires several days to adequately react, we rely initially on a range of innate defenses, many of which operate by activating parts of the inflammatory network. For ex le, LPS-binding protein (LBP) can transfer the LPS of Gram-negative bacteria to CD14 on the surface of macrophages, and this initiates an inflammatory reaction. However, the importance of this chain of events in infection is unclear. First, the innate system is redundant, and bacteria have many components that may serve as targets for it. Second, LBP can transfer LPS to other acceptors that do not induce inflammation. In this study, we show that innate defense against a lethal peritoneal infection with Salmonella requires a direct proinflammatory involvement of LBP, and that this is a major nonredundant function of LBP in this infection model. This emphasizes that blocking the LBP-initiated inflammatory cascade disables an essential defense pathway. Any anti-inflammatory protection that may be achieved must be balanced against the risks inherent in blinding the innate system to the presence of Gram-negative pathogens.
Publisher: Oxford University Press (OUP)
Date: 07-2008
DOI: 10.1086/588711
Publisher: Wiley
Date: 2020
DOI: 10.1002/CTI2.1144
Publisher: Wiley
Date: 20-12-2006
No related grants have been discovered for Gabriela Minigo.