title: Regulation of tumor necrosis factor alpha and its specific receptors during Toxoplasma gondii infection in human monocytic cells.
abstract: The coccidian Toxoplasma gondiiis 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-alpha) acts synergistically with gamma interferon (IFN-gamma) and plays a major role in host cell resistance. We have previously reported that TNF-alpha production induced by IFN-gamma/LPS decreases after T. gondii infection of human myelomonocytic THP-1 cells. Here, we investigated the regulation of TNF-alpha and its specific receptors during T. gondii infection of THP-1 cells. We found that TNF-alpha 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-alpha 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-alpha during the infection process, but also in signal transduction mediated mainly by TNF receptor I.
authors.affiliation: Laboratoire de Parasitologie-Mycologie, UPRES EA-2070, IFR 53-Biomolécules, Université de Reims, 51096 Reims Cedex, France.
authors.forename: A
authors.initials: A
authors.lastname: Belloni
authors.forename: I
authors.initials: I
authors.lastname: Villena
authors.forename: J E
authors.initials: JE
authors.lastname: Gomez
authors.forename: H
authors.initials: H
authors.lastname: Pelloux
authors.forename: A
authors.initials: A
authors.lastname: Bonhomme
authors.forename: M
authors.initials: M
authors.lastname: Guenounou
authors.forename: J M
authors.initials: JM
authors.lastname: Pinon
authors.forename: D
authors.initials: D
authors.lastname: Aubert
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D009000:Monocytes / Q000378:metabolism / Q000469:parasitology*; D011480:Protease Inhibitors / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014122:Toxoplasma / Q000254:growth & development / Q000472:pathogenicity*; D014123:Toxoplasmosis / Q000276:immunology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D011480:Protease Inhibitors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma