Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome.

Autor: Jonathan L Levinsohn, Zachary L Newman, Kristina A Hellmich, Rasem Fattah, Matthew A Getz, Shihui Liu, Inka Sastalla, Stephen H Leppla, Mahtab Moayeri
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS Pathogens, Vol 8, Iss 3, p e1002638 (2012)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1002638
Popis: NOD-like receptor (NLR) proteins (Nlrps) are cytosolic sensors responsible for detection of pathogen and danger-associated molecular patterns through unknown mechanisms. Their activation in response to a wide range of intracellular danger signals leads to formation of the inflammasome, caspase-1 activation, rapid programmed cell death (pyroptosis) and maturation of IL-1β and IL-18. Anthrax lethal toxin (LT) induces the caspase-1-dependent pyroptosis of mouse and rat macrophages isolated from certain inbred rodent strains through activation of the NOD-like receptor (NLR) Nlrp1 inflammasome. Here we show that LT cleaves rat Nlrp1 and this cleavage is required for toxin-induced inflammasome activation, IL-1 β release, and macrophage pyroptosis. These results identify both a previously unrecognized mechanism of activation of an NLR and a new, physiologically relevant protein substrate of LT.
Databáze: Directory of Open Access Journals
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