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First published online September 26, 2003

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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-B, 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-B by showing that T. gondii infection produces an `anti-apoptotic' gene expression profile in wild-type cells but not in the NF-B-null cells. They then pin down the mechanism, demonstrating that T. gondii stimulates phosphorylation of the NF-B inhibitor I-B and, consequently, nuclear translocation of NF-B. Perhaps the most interesting finding, however, is that I-B becomes sequestered on the PV membrane in infected cells. This suggests that T. gondii has developed a novel mechanism for manipulating host NF-B signalling that ensures its survival.

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Related articles in JCS:

Inhibition of caspase activation and a requirement for NF-B function in the Toxoplasma gondii-mediated blockade of host apoptosis

T. Matthew Payne, Robert E. Molestina, and Anthony P. Sinai
JCS 2003 116: 4345-4358. [Abstract] [Full Text]  

Activation of NF-B by Toxoplasma gondii correlates with increased expression of antiapoptotic genes and localization of phosphorylated IB to the parasitophorous vacuole membrane

Robert E. Molestina, T. Matthew Payne, Isabelle Coppens, and Anthony P. Sinai
JCS 2003 116: 4359-4371. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?