Death-defying Toxoplasma

Toxoplasma gondii is an intracellular parasite that produces an asymptomatic infection in healthy individuals but is life threatening to the immunocompromised. The parasite develops in specialized parasitophorous vacuoles (PVs), and part of its survival strategy is to inhibit host cell apoptosis. Anthony Sinai and co-workers now reveal how it does this. On p. 4345, they show that T. gondii inhibits the host apoptotic machinery at multiple levels, including activation of caspases (enzymes that initiate the apoptotic programme). They demonstrate that the parasite cannot do this in cells lacking a subunit of the transcription factor NF-κB, which is part of a pro-survival pathway T. gondii must normally activate. In an accompanying paper (see p. 4359), Sinai and co-workers provide further evidence for the importance of host NF-κB by showing that T. gondii infection produces an `anti-apoptotic' gene expression profile in wild-type cells but not in the NF-κB-null cells. They then pin down the mechanism, demonstrating that T. gondii stimulates phosphorylation of the NF-κB inhibitor I-κB and, consequently, nuclear translocation of NF-κB. Perhaps the most interesting finding, however, is that I-κB becomes sequestered on the PV membrane in infected cells. This suggests that T. gondii has developed a novel mechanism for manipulating host NF-κB signalling that ensures its survival.