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GEN3VA Reports for these tags

PATHOGENS_BD2K_LINCS_DCIC_COURSERA

SOFT file
Title / Description CD8 T cells induce perforin-dependent pathology in Leishmania braziliensis infection
Accession GSE43880
Summary The mechanisms that mediate immunopathologic responses in infectious diseases are often less well understood than how the pathogens are controlled. Here, we have investigated what causes increased pathology following infection with the protozoan parasite, Leishmania braziliensis. We focused on CD8 T cells since their presence in leishmanial lesions has been correlated with increased disease. By adoptively transferring CD8 T cells to L. braziliensis infected RAG mice, we found that unregulated CD8 T cells promote severe pathology at the infection site, as well as the development of metastatic lesions in other skin sites. In mice with severe pathology, we visualized CD8 T cells degranulating and lysing L. braziliensis infected cells, and in parallel studies with L. braziliensis patients we confirmed that CD8 T cells within lesions exhibit a cytolytic phenotype. We found that perforin deficient CD8 T cells failed to induce disease, indicating that the increased disease induced by CD8 T cells was due perforin-dependent cytotoxicity. In contrast, although we found that CD8 T cells made both IFN-γ and IL-17, neither of these cytokines is required for the development of pathology. Thus, we show for the first time that immunopathology in leishmaniasis can be mediated by cytolytic CD8 T cells.
Organism Homo sapiens
Platform GPL10558
Normalized False
Parsed SOFT file
Metadata
Differential expression method Characteristic Direction
Cutoff 500
Microbe_id 5660
Microbe_name Leishmania braziliensis
Cell_type skin (CD8 T cells)
Organism human
Visualizations
Principal Component Analysis
Hierarchical clustering
External Links and Downloads
Gene lists Enrichr L1000CDS2 PAEA Crowdsourcing
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