Interleukin-12 p40- and Fas ligand-dependent apoptotic pathways involving STAT-1 phosphorylation are triggered during infection with a virulent strain of Toxoplasma gondii.

作者: L. Cristina Gavrilescu , Eric Y. Denkers

DOI: 10.1128/IAI.71.5.2577-2583.2003

关键词: Intracellular parasiteTUNEL assayFas ligandPhosphorylationToxoplasma gondiiCell biologyTranscription factorApoptosisCaspaseBiology

摘要: Toxoplasma gondii is an opportunistic intracellular parasite. Infection with the high-virulence T. 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 binding of fluorescein isothiocyanate-conjugated VAD-FMK, irreversible pan-caspase inhibitor, that parasite-triggered occurs among CD4+, CD8+, B220+, Gr-1+, NK1.1+ splenic populations. Caspases 8 9 were activated during infection, implicating cell surface death receptors mitochondria apoptosis. Induction was absent all populations both interleukin-12 (IL-12) p40- Fas ligand (FasL)-negative mice. STAT-1 phosphorylation correlated onset but absence IL-12 p40 functional FasL, activation this transcription factor failed to occur. The results demonstrate gondii-induced multiple apoptotic pathways, dependent upon may play a role lethal pathology infection.

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