Role of macrophages and {alpha}{beta} T lymphocytes in early interleukin 10 production during Listeria monocytogenes infection

Immunity to intracellular bacteria including Listeria monocytogenesis determined by T_h1 cells and CD8 T cells which produce interferon_h.Here we show that high levels of IL-10 are released by splenocytesfrom mice infected with L. monocytogenes. IL-10 was detectedon day 1 after infection, peaked on day 4, and subsequentlydeclined. Cell separation studies and experiments with RAG-1-deficientmice, which do not possess mature B cells or T cells, revealedthat the macrophage Is the major cellular source of early IL-10production. Elevated IL-10 production in RAG-1 mutants and TCRßmutants, but not in TCR mutants, Is consistent with an inhibitionof macrophage IL-10 release by ß T cells. High IL-10production was also seen after infection with another intracellularbacterium, Mycobacterlum bovis. Since IL-10 Inhibits T_h1 cellresponses, certain pathogens might use induction of this cytokineas an evasion mechanism from the protective Immune responseof the host. However, our findings showing high levels of IL-10production in infectious models which are dominated by T_h1 cellresponses suggest that IL-10 alone is insufficient for directingT_h0 differentiation into the T_h2 cell pathway. These findingstherefore challenge the view of IL-10 as a unique and decisivedetermlnator of the T_h2 cell pathway.