IL-10 from macrophages and granulocytes is not required for chronic disease in Leishmania mexicana infection (56.8)

Abstract

Abstract Chronic disease of mice caused by the protozoan parasite Leishmania mexicana requires IL-10 and FcγRIII. Immune complexes consisting of IgG bound to the surface of Leishmania amastigotes can induce IL-10 and suppress IL-12 production from macrophages in vitro. We have found that IgG1 and IgG2a/c can each efficiently induce IL-10 from macrophages, whereas in vivo, mice that lack IgG1 and have stronger and earlier IgG2a/c responses, are more resistant to L. mexicana infection. This calls into question the crucial role of macrophages as the source of IL-10 required for chronic disease. We now show that tissue-specific IL-10-deficient mice lacking IL-10 from macrophages and granulocytes still have chronic disease similar to WT C57BL/6 mice. These Lyz2-cre-IL-10fl/fl mice clearly lack IL-10 from macrophages as expected, but have a similar course of infection and parasite loads as the WT mice. This shows more directly that macrophage IL-10 is not required for chronic disease and that neutrophils are also not a required source of IL-10. Prior work showed that depletion of CD25+CD4+ T cells also produced no major change in chronic disease and that T cell IL-10 in lymph nodes did not differ in mice that heal (such as FcγRIII KO mice) and those that have chronic disease (WT mice). This leaves an open question as to the important source of IL-10, likely in lesions rather than in the lymph node.