IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c+ Cell Populations during Visceral Leishmaniasis |
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Authors: | Benjamin M J Owens Lynette Beattie John W J Moore Najmeeyah Brown Jason L Mann Jane E Dalton Asher Maroof Paul M Kaye |
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Institution: | Centre for Immunology & Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom.;National Institute for Medical Research, United Kingdom |
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Abstract: | IL-10 is a critical regulatory cytokine involved in the pathogenesis of visceral leishmaniasis caused by Leishmania donovani and clinical and experimental data indicate that disease progression is associated with expanded numbers of CD4+ IFNγ+ T cells committed to IL-10 production. Here, combining conditional cell-specific depletion with adoptive transfer, we demonstrate that only conventional CD11chi DCs that produce both IL-10 and IL-27 are capable of inducing IL-10-producing Th1 cells in vivo. In contrast, CD11chi as well as CD11cint/lo cells isolated from infected mice were capable of reversing the host protective effect of diphtheria toxin-mediated CD11c+ cell depletion. This was reflected by increased splenomegaly, inhibition of NO production and increased parasite burden. Thus during chronic infection, multiple CD11c+ cell populations can actively suppress host resistance and enhance immunopathology, through mechanisms that do not necessarily involve IL-10-producing Th1 cells. |
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