IL-10-Producing Th1 Cells and Disease Progression Are Regulated by Distinct CD11c+ Cell Populations during Visceral Leishmaniasis

PLoS Pathogens

Lynette Beattie¹  Najmeeyah Brown¹  Benjamin M. J. Owens¹  John W. J. Moore¹  Jane E. Dalton¹  Jason L. Mann¹  Asher Maroof¹ 

[1] Centre for Immunology & Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom

关键词: T cells;    Parasitic diseases;    Leishmania donovani;    Cytokines;    Neutrophils;    T helper cells;    Splenomegaly;    Cytotoxic T cells;   

DOI  :  10.1371/journal.ppat.1002827

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY