Inhibitory effect of interferon-gamma activated ovine umbilical vein endothelial cells on the intracellular replication of Toxoplasma gondii.
Toxoplasma gondii is an obligate intracellular parasite that is a major cause of abortion and neonatal mortality in sheep. In congenital toxoplasmosis, T gondii first invades the umbilical vein endothelial cells and are then disseminated throughout the fetus. Treatment of ovine umbilical vein endothelial cells with bovine recombinant gamma-interferon (IFN-gamma) blocked the growth of T gondii. Growth of the parasite was measured by 3H-uracil incorporation 18 h after the onset of the infection and by microscopic enumeration of parallel cultures. This assay revealed that when the cells were pretreated with IFN-gamma in concentrations ranging from 0.15-1,250 U/mL, a high degree of inhibition of T gondii replication was observed with the effect being dose-dependent. Maximum activation was achieved by incubating with 625 U/mL IFN-gamma and no activity was present at 0.15 U/mL. This technique could be of relevance as a first line of defense against congenital ovine Toxoplasma infection. Inhibition of T gondii replication is due to a different mechanism from that existing in mouse macrophages and human fibroblasts. L-Arginine-dependent production of reactive nitrogen and oxygen intermediates was not responsible for the inhibition of T gondii replication. Supplements of five amino acids were able to overcome the inhibition partially but significantly. The mechanism of the inhibition remains to be elucidated.
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CJF INSERM 93-09 Immunologie des maladies infectieuses, UFR des sciences pharmaceutiques, Tours, France.
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D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology*; D005347:Fibroblasts / Q000276:immunology / Q000469:parasitology; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D051379:Mice; D016053:RNA, Protozoan / Q000096:biosynthesis; D011994:Recombinant Proteins; D012756:Sheep; D012757:Sheep Diseases; D014122:Toxoplasma / Q000254:growth & development / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000276:immunology; D014364:Tryptophan / Q000494:pharmacology; D014471:Umbilical Veins; D014498:Uracil / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000596:Amino Acids; D016053:RNA, Protozoan; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D014498:Uracil; D007371:Interferon-gamma; D014364:Tryptophan; D001120:Arginine