The Journal of Experimental Medicine
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Published online 17 January 2006 doi:10.1084/jem.20052288
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 1, 177-188
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ARTICLE

 Uptake of Leishmania major by dendritic cells is mediated by Fc{gamma} receptors and facilitates acquisition of protective immunity

Florian Woelbing1, Susanna Lopez Kostka1, Katharina Moelle1, Yasmine Belkaid3, Cord Sunderkoetter5, Sjef Verbeek6, Ari Waisman2, Axel P. Nigg1, Juergen Knop1, Mark C. Udey4, and Esther von Stebut1

1 Department of Dermatology and 2 Section for Pathophysiology, First Department of Internal Medicine, Johannes Gutenberg-University, Mainz 55131, Germany
3 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases and 4 Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
5 Department of Dermatology, University of Münster, Münster 48129, Germany
6 Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden 2300, Netherlands

CORRESPONDENCE Esther von Stebut: vonstebu{at}mail.uni-mainz.de

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.

Abbreviations used: BMDC, bone marrow–derived DC; CFSE, carboxyl fluorescein succinimidyl ester; CR3, complement receptor 3; IS, immune serum; M{Phi}, macrophages; NMS, normal mouse serum; SLA, soluble Leishmania antigen.

F. Woelbing and S.L. Kostka contributed equally to this paper.


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