Anthrax Lethal Factor Cleavage of Nlrp1 Is Required for Activation of the Inflammasome

作者：Levinsohn Jonathan L^*; Newman Zachary L; Hellmich Kristina A; Fattah Rasem; Getz Matthew A; Liu Shihui; Sastalla Inka; Leppla Stephen H; Moayeri Mahtab

来源：PLoS Pathogens, 2012, 8(3): e1002638.

DOI：10.1371/journal.ppat.1002638

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-1 beta 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 beta 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.

• 出版日期2012-3