TOXOPLASMA GONDII-INFECTED CELLS ARE RESISTANT TO MULTIPLE INDUCERS OF APOPTOSIS

Infection with certain intracellular pathogens, including viruses and bacteria, may induce host cell apoptosis. On the other hand, infection with some viruses inhibits apoptosis, Complex protozoan parasites, in cluding Toxoplasma gondii and members of Plasmodium, Leishmania, and M icrosporidia, are also obligate intracellular pathogens, get relativel y little is known regarding their subversion of host cell functions. W e now report that cells infected with T. gondii are resistant to multi ple inducers of apoptosis, including Fas-dependent and Fas-independent CTL-mediated cytotoxicity, IL-2 deprivation, gamma irradiation, UV ir radiation, and the calcium ionophore beauvericin. Inhibition of such a broad array of apoptosis inducers suggests that a mechanism common to many, or perhaps all, apoptotic pathways is involved. The inhibitory activity requires live intracellular parasite and ongoing protein synt hesis. Despite T. gondii-mediated inhibition of DNA fragmentation, inf ected cells can still be lysed by CTL.