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

被引：254

作者：

Levinsohn, Jonathan L. ^{[1
]}

Newman, Zachary L. ^{[1
]}

Hellmich, Kristina A. ^{[1
]}

Fattah, Rasem ^{[1
]}

Getz, Matthew A. ^{[1
]}

Liu, Shihui ^{[1
]}

Sastalla, Inka ^{[1
]}

Leppla, Stephen H. ^{[1
]}

Moayeri, Mahtab ^{[1
]}

机构：

[1] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA

来源：

PLOS PATHOGENS | 2012年 / 8卷 / 03期

关键词：

CASPASE-1; ACTIVATION; TOXIN; PROTEOLYSIS; KINASE;

D O I：

10.1371/journal.ppat.1002638

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：7

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