Open AccessInterleukin-12 p40- and Fas Ligand-Dependent Apoptotic Pathways Involving STAT-1 Phosphorylation Are Triggered during Infection with a Virulent Strain ofToxoplasma gondii
Author(s) -
L. Cristina Gavrilescu,
Eric Denkers
Publication year - 2003
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.71.5.2577-2583.2003
Subject(s) - biology , fas ligand , toxoplasma gondii , apoptosis , tunel assay , caspase , cytokine , programmed cell death , microbiology and biotechnology , immunology , antibody , biochemistry
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.