c-fos and tumor necrosis factor gene expression in Leishmania donovani-infected macrophages.

Leishmania donovani is an obligate intracellular protozoan which resides in macrophages and impairs a number of macrophage functions. We have undertaken to study this host cell-parasite interaction by examining the ability of L. donovani to impair the transmission of information from the cell surface to the nucleus and thus influence normal gene expression. We demonstrate that, in response to lipopolysaccharide, expression of both the c-fos and tumor necrosis factor genes was impaired in L. donovani-infected macrophages. Indomethacin reversed the parasite-mediated downregulation of the tumor necrosis factor gene but not the c-fos gene, suggesting that the impaired expression of these two genes occurred through different mechanisms. Direct stimulation of protein kinase C with oleoyl-2-acetoyl-3-glycerol did not abrogate inhibition of c-fos gene expression by L. donovani; however, L929 cell-conditioned medium induced a similar level of c-fos gene expression in both infected and noninfected macrophages. Impairment of c-fos gene expression by L. donovani thus appeared to be selective, depending on the external stimuli used to induce its expression. These data argue that L. donovani was capable of impairing macrophage gene expression in a selective rather than a general manner.