ROLE OF MACROPHAGES AND ALPHA-BETA-T-LYMPHOCYTES IN EARLY INTERLEUKIN-10 PRODUCTION DURING LISTERIA-MONOCYTOGENES INFECTION

Immunity to intracellular bacteria including Listeria monocytogenes is determined by T(h)1 cells and CD8 T cells which produce interferon-gamma. Here we show that high levels of IL-10 are released by splenocytes from mice infected with L. monocytogenes. IL-10 was detected on day 1 after infection, peaked on day 4, and subsequently declined. Cell separation studies and experiments with RAG-1-deficient mice, which do not possess mature B cells or T cells, revealed that the macrophage is the major cellular source of early IL-10 production. Elevated IL-10 production in RAG-1 mutants and TCRbeta mutants, but not in TCRdelta mutants, is consistent with an inhibition of macrophage IL-10 release by alphabeta T cells. High IL-10 production was also seen after infection with another intracellular bacterium, Mycobacterium bovis. Since IL-10 inhibits T(h)1 cell responses, certain pathogens might use induction of this cytokine as an evasion mechanism from the protective immune response of the host. However, our findings showing high levels of IL-10 production in infectious models which are dominated by T(h)1 cell responses suggest that IL-10 alone is insufficient for directing T(h)0 differentiation into the T(h)2 cell pathway. These findings therefore challenge the view of IL-10 as a unique and decisive determinator of the T(h)2 cell pathway.