| 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
(Affiliation: Department of Dermatology and 2Section for Pathophysiology, First Department of Internal Medicine, Johannes Gutenberg-University, Mainz 55131, Germany.)
|
| Journal | The Journal of experimental medicine
(J Exp Med)
Vol. 203
Issue 1
Pg. 177-88
(Jan 23 2006)
ISSN: 0022-1007 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)
|
