Project description:Proteomic characterization of complexity and dynamics of detergent resistant membranes of sexual and asexual stages of the rodent malaria parasite Plasmodium berghei
Project description:Infection of C57BL/6 mice with Plasmodium berghei ANKA (PbA) is a well-established experimental model of cerebral malaria (ECM). ECM is characterised by high levels of parasite sequestration and recruitment of pathogenic CD8+ T cells to the brain. The role of CD4+ T cells in this model has not yet been fully elucidated, although our laboratory has recently shown that CD4+ T cell depletion prior to infection results in significantly lower parasite burdens and protection from ECM. These data highlight a pathogenic role for CD4+ T cells in ECM. Our unpublished observations indicate that mice lacking the CD8+ T cell cytolytic effector molecule, Granzyme B, (GzmB), are resistant to ECM, showing markedly reduced parasite burdens. Late depletion of CD4+ T cells from PbA-infected GzmB-deficient mice results in enhanced parasite burdens, indicating that these cells may play an anti-parasitic role. In the present study, we have analysed splenic CD4+ T cell gene expression profiles in naïve C57BL/6 mice, and PbA-infected wild-type and GzmB-deficent mice to further our understanding of the CD4+ T cell response in ECM.
Project description:Background: The mosquito Anopheles gambiae is a major vector of human malaria. Increasing evidence indicates that blood cells (hemocytes) comprise an essential arm of the mosquito innate immune response against both bacteria and malaria parasites. To further characterize the role of hemocytes in mosquito immunity, we undertook the first genome-wide transcriptomic analyses of adult female An. gambiae hemocytes following infection by two species of bacteria and a malaria parasite. Results: We identified 4047 genes expressed in hemocytes, using An. gambiae genome-wide microarrays. While 279 transcripts were significantly enriched in hemocytes relative to whole adult female mosquitoes, 959 transcripts exhibited immune challenge-related regulation. The global transcriptomic responses of hemocytes to challenge with different species of bacteria and/or different stages of malaria parasite infection revealed discrete, minimally overlapping, pathogen-specific signatures of infection-responsive gene expression; 105 of these represented putative immunity-related genes including anti-Plasmodium factors. Of particular interest was the specific co-regulation of various members of the Imd and JNK immune signaling pathways during malaria parasite invasion of the mosquito midgut epithelium. Conclusion: Our genome-wide transcriptomic analysis of adult mosquito hemocytes reveals pathogen-specific signatures of gene regulation and identifies several novel candidate genes for future functional studies.
Project description:Infection of C57BL/6 mice with Plasmodium berghei ANKA (PbA) is a well-established experimental model of cerebral malaria (ECM). ECM is characterised by high levels of parasite sequestration and recruitment of pathogenic CD8+ T cells to the brain. The role of CD4+ T cells in this model has not yet been fully elucidated, although our laboratory has recently shown that CD4+ T cell depletion prior to infection results in significantly lower parasite burdens and protection from ECM. These data highlight a pathogenic role for CD4+ T cells in ECM. Our unpublished observations indicate that mice lacking the CD8+ T cell cytolytic effector molecule, Granzyme B, (GzmB), are resistant to ECM, showing markedly reduced parasite burdens. Late depletion of CD4+ T cells from PbA-infected GzmB-deficient mice results in enhanced parasite burdens, indicating that these cells may play an anti-parasitic role. In the present study, we have analysed splenic CD4+ T cell gene expression profiles in naïve C57BL/6 mice, and PbA-infected wild-type and GzmB-deficent mice to further our understanding of the CD4+ T cell response in ECM. Splenic CD4 T cells isolated by cell sorting from either uninfected C57BL/6 or PbA-infected C57BL/6 or B6.GzmB-/- mice at day 4 post-infection. Total RNA obtained from four mice per group.
Project description:The studies reported here were designed to define in more detail the effector cells responsible for the transfer of protective immunity to young host against P. berghei infection, and to investigate the genes expressed in spleen cells of adult protected rats capable of transferring protection to young rats. Keywords: age, malaria, protection, rat
Project description:The aim of this study is to characterise gene expression in the rodent malaria intra-erthrocytic development cycle. This will inform two further studies looking at host-parasite interactions in rodent malaria and in comparison to the same stage of human malaria will provide insight into variation in lifecycles between human and rodent malaria. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
Project description:During the progress through its complex life cycle, the malaria parasite requires strict control of gene expression but the mechanism controlling this process remain poorly understood and unexplored for therapeutic purposes. A group of the apicomplexa-specific putative transcription factors with AP2 DNA binding domain (apiAP2) has been identified as the major regulators of the parasite transcriptome at multiple stages. The targets and the role of the majority of the members of the family however are unknown.