Open AccessDirect inhibition of cytochrome c ‐induced caspase activation in vitro by Toxoplasma gondii reveals novel mechanisms of interference with host cell apoptosis
Author(s) -
Keller Philine,
Schaumburg Frieder,
Fischer Silke F.,
Häcker Georg,
Groß Uwe,
Lüder Carsten G.K.
Publication year - 2006
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.2006.00241.x
Subject(s) - toxoplasma gondii , cytochrome c , biology , microbiology and biotechnology , caspase , intracellular , jurkat cells , apoptosis , extracellular , cytosol , caspase 3 , caspase 2 , intracellular parasite , programmed cell death , biochemistry , t cell , immunology , enzyme , immune system , antibody
The intracellular parasite Toxoplasma gondii is known to inhibit apoptosis of its host cell. The molecular mechanisms of this interference are, however, not yet completely understood. We show here that viable parasites prominently inhibited the activation of caspase 3/7 induced by cytochrome c , dATP and dithiothreitol in cytosolic extracts of human‐derived Jurkat leukemic T cells. In contrast, granzyme B‐induced caspase activity was only slightly diminished. De novo protein biosynthesis by T. gondii was dispensable for the inhibition of cytochrome c ‐induced caspase activation. Furthermore, a complete parasite lysate or, more importantly, molecules released by extracellular parasites mediated the interaction with the caspase cascade. The cell‐free system applied here is thus a valuable tool to study the interaction of T. gondii and possibly other intracellular pathogens with host cell apoptosis.