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The Journal of Immunology, 1998, 160: 1824-1830.
Copyright © 1998 by The American Association of Immunologists

Toxoplasma gondii-Infected Cells Are Resistant to Multiple Inducers of Apoptosis1

Paul B. Nash2,*, Matthew B. Purner*, Ronald P. Leon*, Penelope Clarke*, Richard C. Duke{dagger} and Tyler J. Curiel2,*,{dagger}

* Department of Medicine, Division of Infectious Disease, and {dagger} Department of Medicine, Division of Medical Oncology, University of Colorado Health Sciences Center, Denver, CO 80220

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, including Toxoplasma gondii and members of Plasmodium, Leishmania, and Microsporidia, are also obligate intracellular pathogens, yet relatively little is known regarding their subversion of host cell functions. We now report that cells infected with T. gondii are resistant to multiple inducers of apoptosis, including Fas-dependent and Fas-independent CTL-mediated cytotoxicity, IL-2 deprivation, gamma irradiation, UV irradiation, 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 synthesis. Despite T. gondii-mediated inhibition of DNA fragmentation, infected cells can still be lysed by CTL.




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