TY - JOUR
T1 - Uptake of Leishmania major by dendritic cells is mediated by Fcγ receptors and facilitates acquisition of protective immunity
AU - Woelbing, Florian
AU - Kostka, Susanna Lopez
AU - Moelle, Katharina
AU - Belkaid, Yasmine
AU - Sunderkoetter, Cord
AU - Verbeek, Sjef
AU - Waisman, Ari
AU - Nigg, Axel P.
AU - Knop, Juergen
AU - Udey, Mark C.
AU - Von Stebut, Esther
PY - 2006/1/23
Y1 - 2006/1/23
N2 - 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.Φ) 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 FcγRI and FcγRIII. 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 Fcγ-/- mice contained fewer parasite-infected DCs in vivo. Infected B cell-deficient mice as well as Fcγ-/- 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-γ production, and these deficits were normalized by infection with IgG-opsonized parasites. These data demonstrate that DC and MΦ use different receptors to recognize and ingest L. major with different outcomes, and indicate that B cell-derived, parasite-reactive IgG and DC FcγRI and FcγRIII are essential for optimal development of protective immunity. JEM
AB - 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.Φ) 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 FcγRI and FcγRIII. 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 Fcγ-/- mice contained fewer parasite-infected DCs in vivo. Infected B cell-deficient mice as well as Fcγ-/- 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-γ production, and these deficits were normalized by infection with IgG-opsonized parasites. These data demonstrate that DC and MΦ use different receptors to recognize and ingest L. major with different outcomes, and indicate that B cell-derived, parasite-reactive IgG and DC FcγRI and FcγRIII are essential for optimal development of protective immunity. JEM
UR - http://www.scopus.com/inward/record.url?scp=31344442771&partnerID=8YFLogxK
U2 - 10.1084/jem.20052288
DO - 10.1084/jem.20052288
M3 - Article
C2 - 16418399
AN - SCOPUS:31344442771
SN - 0022-1007
VL - 203
SP - 177
EP - 188
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 1
ER -