INTERFERON-GAMMA-ACTIVATED PRIMARY ENTEROCYTES INHIBIT TOXOPLASMA-GONDII REPLICATION - A ROLE FOR INTRACELLULAR IRON

Toxoplasma gondii is an obligate intracellular parasite that infects a wide variety of nucleated cells in its numerous intermediate hosts in cluding man. The oral route is the natural portal of entry of T. gondi i. Ingested organisms are released from cysts or oocysts within the ga strointestinal tract and initially invade the intestinal epithelium. W e show that T. gondii invades and proliferates in cultured primary rat enterocytes, obtained with an original procedure. Activation of the e nterocytes with rat recombinant interferon-gamma (IFN-gamma) inhibits T. gondii replication, the inhibition being dose dependent. Neither ni trogen and oxygen derivatives nor tryptophan starvation appear to be i nvolved in the inhibition of parasite replication by IFN-gamma. Experi ments using Fe2+ salt, carrier and chelator indicate that intracellula r T gondii replication is iron dependent, suggesting that IFN-gamma-tr eated enterocytes inhibit T. gondii replication by limiting the availa bility of intracellular iron to the parasite. Our data show that enter ocytes probably play a major role on mucosal surfaces as a first line of defence against this coccidia, and possibly other pathogens, throug h an immune mechanism. The results suggest that limiting the availabil ity of iron could represent a broad antimicrobial mechanism through wh ich the activated enterocytes exert control over intracellular pathoge ns.