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Infect. Immun. doi:10.1128/IAI.00316-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

FcRIII mediates IgG-induced IL-10 and is required for chronic Leishmania lesions

Department of Medicine, Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA, VA Medical Center, Philadelphia, PA, 19104

^* To whom correspondence should be addressed. Email: buxbaum{at}mail.med.upenn.edu.

	Abstract

FcR and IL-10 are both required for chronic disease in C57BL/6 mice with Leishmania mexicana parasite infection. FcR is a component of several different FcRs and may be a component of some T cell receptors. The initial antibody response to L. mexicana is an IgG1 response, and IgG1 preferentially binds to FcRIII in other systems. To begin to dissect the mechanisms by which FcRs contribute to chronic disease, we infected FcRIII KO mice with L. mexicana. We show that FcRIII KO mice are resistant to L. mexicana infection, resolving lesions in association with a stronger IFN- response, similar to IL-10 KO mice, with parasite control by 12 weeks. We found that the Leishmania-specific IgG response is unaltered in FcRIII KO mice as compared with wild-type controls. The frequency of IL-10 production from lymph node CD25⁺CD4⁺ T cells is the same in KO and wild-type mice and depletion of CD25⁺ cells did not alter the course of infection, implying that T_reg cells may not be the mechanism for susceptibility to L. mexicana infection, unlike L. major infection. However, IL-10 mRNA was greatly diminished in the lesions of FcRIII KO mice as compared to B6 controls. Furthermore, macrophages from FcRIII KO and FcR KO mice have the same profound defect in IL-10 production induced by IgG-opsonized amastigotes. We also found IL-10-dependent (major) and independent (minor) inhibition of IL-12-mediated by FcRIII, as well as parasite-mediated inhibition of IL-12 and induction of IL-10, independent of FcR. Our data demonstrate a specific role for FcRIII in suppressing protective immunity in L. mexicana infection, likely through macrophage IL-10 production in the lesion.