INHIBITION OF TOXOPLASMA-GONDII REPLICATION IN IFN-GAMMA-ACTIVATED HUMAN INTESTINAL EPITHELIAL-CELLS

Toxoplasma gondii is an obligate intracellular parasite which is respo nsible for severe disease after congenital infection and in immunocomp romised patients, for which there is no effective therapy. In acquired toxoplasmosis, T. gondii first invade enterocytes and are disseminate d 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]-u racil incorporation assays 18 h after infection. This assay showed tha t when cells were pretreated with IFN-gamma concentrations ranging fro m 2.5 to 5000 U/mL, a high degree of inhibition of T. gondii replicati on could be observed, with the effect being dose dependent. This could be of relevance as a first line of defence against human Toxoplasma i nfection. Inhibition is due to a different mechanism from that existin g in mouse macrophages and human fibroblasts: L-arginine-dependent pro duction of reactive nitrogen intermediates, reactive oxygen intermedia tes synthesis or production of indoleamine 2,3 dioxygenase were not re sponsible for inhibition of T. gondii proliferation.