Uptake of Leishmania major by dendritic cells is mediated by Fcγ receptors and facilitates acquisition of protective immunity

Uptake of Leishmania major by dendritic cells (DCs) results in activation and interleukin (IL)-12 release. Infected DCs efficiently stimulate CD4(+) and CD8(+) T cells and vaccinate against leishmaniasis. In contrast, complement receptor 3-dependent phagocytosis of L. major by macrophages (M Phi) leads exclusively to MHC class II-restricted antigen presentation to primed, but not naive, T cells, and no IL-12 production. Herein, we demonstrate that uptake of L. major by DCs required parasite-reactive immunoglobulin (Ig) G and involved Fc gamma RI and Fc gamma RIII. In vivo, DC infiltration of L. major-infected skin lesions coincided with the appearance of antibodies in sera. Skin of infected B cell-deficient mice and Fc gamma(-/-) mice contained fewer parasite-infected DCs in vivo. Infected B cell-deficient mice as well as Fc gamma(-/-) mice (all on the C57BL/6 background) showed similarly increased disease susceptibility as assessed by lesion volumes and parasite burdens. The B cell-deficient mice displayed impaired T cell priming and dramatically reduced IFN gamma production, and these deficits were normalized by infection with IgG-opsonized parasites. These data demonstrate that DC and M Phi use different receptors to recognize and ingest L. major with different outcomes, and indicate that B cell-derived, parasite-reactive IgG and DC Fc gamma RI and Fc gamma RIII are essential for optimal development of protective immunity.