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Infection and Immunity, May 2003, p. 2577-2583, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2577-2583.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Interleukin-12 p40- and Fas Ligand-Dependent Apoptotic Pathways Involving STAT-1 Phosphorylation Are Triggered during Infection with a Virulent Strain of Toxoplasma gondii

L. Cristina Gavrilescu and Eric Y. Denkers^*

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401

Received 27 November 2002/ Returned for modification 9 January 2003/ Accepted 23 January 2003

Toxoplasma gondii is an opportunistic intracellular parasite. Infection with the high-virulence T. gondii strain RH induces inflammatory cytokine overproduction and uncontrolled apoptosis in lymphoid organs. Here, we show by fluorescent terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and binding of fluorescein isothiocyanate-conjugated VAD-FMK, an irreversible pan-caspase inhibitor, that parasite-triggered apoptosis occurs among CD4⁺, CD8⁺, B220⁺, Gr-1⁺, and NK1.1⁺ splenic populations. Caspases 8 and 9 were activated during infection, implicating cell surface death receptors and mitochondria in apoptosis. Induction of apoptosis was absent among all cell populations in both interleukin-12 (IL-12) p40- and Fas ligand (FasL)-negative mice. STAT-1 phosphorylation correlated with onset of apoptosis during infection, but in the absence of IL-12 p40 and functional FasL, activation of this transcription factor failed to occur. The results demonstrate T. gondii-induced activation of multiple apoptotic pathways, dependent upon both IL-12 p40 and FasL, that may play a role in the lethal pathology of infection.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401. Phone: (607) 253-4022. Fax: (607) 253-3384. E-mail: eyd1{at}cornell.edu.

Editor: J. M. Mansfield

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Infection and Immunity, May 2003, p. 2577-2583, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2577-2583.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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