title: Uptake of Leishmania major by dendritic cells is mediated by Fcgamma receptors and facilitates acquisition of protective immunity.
abstract: 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 (MPhi) 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 FcgammaRI and FcgammaRIII. 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 Fcgamma-/- mice contained fewer parasite-infected DCs in vivo. Infected B cell-deficient mice as well as Fcgamma-/- 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 MPhi use different receptors to recognize and ingest L. major with different outcomes, and indicate that B cell-derived, parasite-reactive IgG and DC FcgammaRI and FcgammaRIII are essential for optimal development of protective immunity.
authors.affiliation: Department of Dermatology and 2Section for Pathophysiology, First Department of Internal Medicine, Johannes Gutenberg-University, Mainz 55131, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Woelbing
authors.forename: Susanna Lopez
authors.initials: SL
authors.lastname: Kostka
authors.forename: Katharina
authors.initials: K
authors.lastname: Moelle
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: Cord
authors.initials: C
authors.lastname: Sunderkoetter
authors.forename: Sjef
authors.initials: S
authors.lastname: Verbeek
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Axel P
authors.initials: AP
authors.lastname: Nigg
authors.forename: Juergen
authors.initials: J
authors.lastname: Knop
authors.forename: Mark C
authors.initials: MC
authors.lastname: Udey
authors.forename: Esther
authors.initials: E
authors.lastname: von Stebut
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology; D007074:Immunoglobulin G / Q000276:immunology; D018320:Leishmania major / Q000276:immunology* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D016177:Macrophage-1 Antigen / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D016177:Macrophage-1 Antigen; D017452:Receptors, IgG