Inhibition of Toxoplasma gondii replication in IFN-gamma-activated human intestinal epithelial cells

Toxoplasma gondii is an obligate intracellular parasite which is responsible for severe disease after congenital infection and in immunocompromised patients, for which there is no effective therapy. In acquired toxoplasmosis, T. gondii first invade enterocytes and are disseminated throughout the body. Treatment of the adherent human intestinal cell line CaCO2 with recombinant human IFN-gamma inhibited the replication of T. gondii. Growth of the parasite was measured in vitro by [H-3]-uracil incorporation assays 18 h after infection. This assay showed that when cells were pretreated with IFN-gamma concentrations ranging from 2.5 to 5000 U/mL, a high degree of inhibition of T. gondii replication could be observed, with the effect being dose dependent. This could be of relevance as a first line of defence against human Toxoplasma infection. Inhibition is due to a different mechanism from that existing in mouse macrophages and human fibroblasts: L-arginine-dependent production of reactive nitrogen intermediates, reactive oxygen intermediates synthesis or production of indoleamine 2,3 dioxygenase were not responsible for inhibition of T. gondii proliferation.