title: Interleukin-10 from T cells, but not macrophages and granulocytes, is required for chronic disease in Leishmania mexicana infection.
abstract: Chronic cutaneous disease of mice caused by the protozoan parasite Leishmania mexicana requires interleukin-10 (IL-10) and FcγRIII (an activating IgG receptor). Macrophages readily secrete IL-10 in response to IgG-coated amastigotes, making macrophages a prime candidate as the critical source of IL-10. However, indirect evidence suggested that macrophage IL-10 is not essential for chronic disease. I now show directly that mice lacking IL-10 from macrophages and granulocytes still have chronic disease, like wild-type C57BL/6 mice. However, T cell-derived IL-10 is required for chronic disease. CD4-cre IL-10flox/flox mice lack IL-10 from T cells (both CD4+ and CD8+) and heal their L. mexicana lesions, with parasite control. I had previously shown that depletion of CD25+ T cells had no effect on chronic disease, and thus, T cells other than CD25+ regulatory T (Treg) cells should be the important source of IL-10. Given that conventional T cells do not express FcγRs, there is likely to be an indirect pathway by which FcγRIII on some other cell engaged by IgG1-amastigote immune complexes induces IL-10 from T cells. Further work is needed to delineate these pathways.
authors.affiliation: Philadelphia Research and Education Foundation, Philadelphia, Pennsylvania, USA, VA Medical Center, Philadelphia, Pennsylvania, USA, and Department of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA buxbaum17@hotmail.com.
authors.forename: Laurence U
authors.initials: LU
authors.lastname: Buxbaum
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics*; D007894:Leishmania mexicana / Q000276:immunology* / Q000472:pathogenicity; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D017452:Receptors, IgG; D016753:Interleukin-10