Interleukin 10- and Fcγ Receptor-Deficient Mice ResolveLeishmania mexicanaLesions

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Abstract
Infection of C57BL/6 (B6) mice withLeishmania mexicanais associated with a minimal immune response and chronic disease. Here we show that B6 interleukin 10−/−(IL-10−/−) mice resolve their lesions and exhibit increased gamma interferon (IFN-γ), nitric oxide production, and delayed-type hypersensitivity. This enhanced resistance was dependent upon IL-12p40, since treatment ofL. mexicana-infected IL-10−/−mice with anti-IL-12p40 monoclonal antibody abrogated healing. Antibody-opsonizedL. mexicanainduced IL-10 production by B6 macrophages in vitro, implicating antibody binding to Fc receptors as a mechanism involved in IL-10 production in this infection. Furthermore, B6 FcRγ−/−mice resolveL. mexicanalesions, and lymph node cells from these mice produced less IL-10 and more IFN-γ than cells from infected wild-type mice. These data demonstrate that removal of IL-10 or FcγR leads to resolution ofL. mexicanadisease and support a model in which ligation of FcγR byL. mexicana-bound immunoglobulin G promotes IL-10 production, leading to chronic disease.