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IgG1 and IgG2a/c induce IL‐10 from different FcγR on macrophages as well as DCs in Leishmania mexicana infection
Author(s) -
Buxbaum Laurence U.,
Thomas Bolaji N.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.674.3
Subject(s) - immune system , opsonin , leishmania mexicana , immunology , biology , macrophage , in vivo , amastigote , leishmania , antibody , in vitro , parasite hosting , biochemistry , microbiology and biotechnology , world wide web , computer science
Chronic L. mexicana disease in C57BL/6 mice requires both FcRγ and IL‐10. The initial response to infection includes anti‐leishmanial IgG1 followed by a chronic phase mixed IgG1/IgG2a/c response. FcγRIII KO and IL‐10 KO mice resolve lesions with a stronger IFN‐γ response, with parasite control by 12 weeks. We also found that bone marrow‐derived macrophages (BMMΦ) from FcγRIII KO and FcRγ KO mice have the same profound defect in IL‐10 production induced by IgG1‐opsonized amastigotes. Previous reports have shown that FcγRI and IV have higher affinity binding of IgG2a/c than other FcγR. We now show that in BMMΦ, IgG1‐opsonized parasites induce IL‐10 primarily via FcγRIII, while IL‐10 induction by IgG2a/c‐opsonized parasites is mostly via FcγRI and to a lesser extent, FcγRIII. Although FcγRIV was present on BMMΦ, blockade of this receptor did not have an effect on IL‐10 induction. Similar results were obtained for BMDCs indicating both macrophages and DCs are equally capable of secreting IL‐10 in response to parasite immune complexes. Furthermore, in vivo we found that although healing FcγRIII KO mice have no alteration in IL‐10 from T cells in the draining LN, there was a 7‐fold decrease in IL‐10 from lesions, where macrophages are abundant and T cells are rare. This supports a role for both IgG1 and IgG2a/c, and macrophages and possibly DCs in generating the suppressive IL‐10 response in the lesion during infection. Funded by VA Merit.