Regulation of tumor necrosis factor alpha and its specific receptors during Toxoplasma gondii infection in human monocytic cells

Abstract.

The coccidian Toxoplasma gondii is an obligate intracellular parasite which can infect all cell types. Among the cytokines elicited by the immune response to Toxoplasma, tumor necrosis factor alpha (TNF-α) acts synergistically with gamma interferon (IFN-γ) and plays a major role in host cell resistance. We have previously reported that TNF-α production induced by IFN-γ/LPS decreases after T. gondii infection of human myelomonocytic THP-1 cells. Here, we investigated the regulation of TNF-α and its specific receptors during T. gondii infection of THP-1 cells. We found that TNF-α production was regulated at a post-transcriptional level and that TNF receptor expression was regulated at a pretranscriptional level. The TNF receptor I shedding and the fall in TNF-α levels observed after T. gondii infection would thus be induced by a parasite component with serine protease activity. These findings indicate that T. gondii participates not only in controlling the cytotoxic effects of TNF-α during the infection process, but also in signal transduction mediated mainly by TNF receptor I.