IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis
AuthorOwens, BMJ; Beattie, L; Moore, JWJ; Brown, N; Mann, JL; Dalton, JE; Maroof, A; Kaye, PM
Source TitlePLoS Pathogens
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sBeattie, Lynette
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsOwens, B. M. J., Beattie, L., Moore, J. W. J., Brown, N., Mann, J. L., Dalton, J. E., Maroof, A. & Kaye, P. M. (2012). IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c(+) Cell Populations during Visceral Leishmaniasis. PLOS PATHOGENS, 8 (7), https://doi.org/10.1371/journal.ppat.1002827.
Access StatusOpen Access
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 CD11c(hi) DCs that produce both IL-10 and IL-27 are capable of inducing IL-10-producing Th1 cells in vivo. In contrast, CD11c(hi) as well as CD11c(int/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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