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: Florian Woelbing, Susanna Lopez Kostka, Katharina Moelle, Yasmine Belkaid, Cord Sunderkoetter, Sjef Verbeek, Ari Waisman, Axel P Nigg, Juergen Knop, Mark C Udey, Esther von Stebut
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 203 Issue 1 Pg. 177-88 (Jan 23 2006) ISSN: 0022-1007 [Print] United States
• PMID: 16418399 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin G
• Macrophage-1 Antigen
• Receptors, IgG

Topics

• Animals
• B-Lymphocytes (immunology)
• Cells, Cultured
• Dendritic Cells (immunology, parasitology)
• Immunoglobulin G (immunology)
• Leishmania major (immunology, pathogenicity)
• Leishmaniasis, Cutaneous (immunology, parasitology, prevention & control)
• Macrophage-1 Antigen (immunology)
• Macrophages (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Phagocytosis
• Receptors, IgG (immunology)