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- Title
IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c<sup>+</sup> Cell Populations during Visceral Leishmaniasis.
- Authors
Owens, Benjamin M. J.; Beattie, Lynette; Moore, John W. J.; Brown, Najmeeyah; Mann, Jason L.; Dalton, Jane E.; Maroof, Asher; Kaye, Paul M.
- 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.
- Subjects
VISCERAL leishmaniasis; INTERLEUKIN-10; T cells; DISEASE progression; LEISHMANIA donovani
- Publication
PLoS Pathogens, 2012, Vol 8, Issue 7, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1002827