Interleukin-10 from T cells, but not macrophages and granulocytes, is required for chronic disease in Leishmania mexicana infection

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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.

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Buxbaum, L. U. (2015). Interleukin-10 from T cells, but not macrophages and granulocytes, is required for chronic disease in Leishmania mexicana infection. Infection and Immunity, 83(4), 1366–1371. https://doi.org/10.1128/IAI.02909-14

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