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

PLoS Pathogens

Jonathan L. Levinsohn¹ 

[1] Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America

关键词: Macrophages;    Inflammasomes;    Sequence motif analysis;    Toxins;    Cell death;    Anthrax;    HT1080 cells;    Protein expression;   

DOI  :  10.1371/journal.ppat.1002638

学科分类：生物科学（综合）

来源: Public Library of Science

【 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-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.

【 授权许可】

CC BY