IL-10-producing Th1 cells and disease progression are regulated by distinct CD11c⁺ cell populations during visceral leishmaniasis.
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.
Centre for Immunology & Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom.
Benjamin M J
BM
Owens
Lynette
L
Beattie
John W J
JW
Moore
Najmeeyah
N
Brown
Jason L
JL
Mann
Jane E
JE
Dalton
Asher
A
Maroof
Paul M
PM
Kaye
D000818:Animals; D039521:CD11c Antigen / Q000032:analysis*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004167:Diphtheria Toxin; D018450:Disease Progression; D016753:Interleukin-10 / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis; D007893:Leishmania donovani / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology*
D039521:CD11c Antigen; D004167:Diphtheria Toxin; D020381:Interleukin-17; D016753:Interleukin-10