0

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, Eric Y Denkers

Infect Immun. 2003 May;71(5):2577-83.

PMID: 12704131

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42415295 Caspase Inhibitor I, Biotin Conjugate Caspase Inhibitor I, Biotin Conjugate Price
qrcode