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Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome
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نویسنده
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levinsohn j.l. ,newman z.l. ,hellmich k.a. ,fattah r. ,getz m.a. ,liu s. ,sastalla i. ,leppla s.h. ,moayeri m.
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منبع
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plos pathogens - 2012 - دوره : 8 - شماره : 3
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چکیده
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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.
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آدرس
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laboratory of parasitic diseases,national institutes of allergy and infectious diseases,national institutes of health,bethesda,md, United States, laboratory of parasitic diseases,national institutes of allergy and infectious diseases,national institutes of health,bethesda,md, United States, laboratory of parasitic diseases,national institutes of allergy and infectious diseases,national institutes of health,bethesda,md, United States, laboratory of parasitic diseases,national institutes of allergy and infectious diseases,national institutes of health,bethesda,md, United States, laboratory of parasitic diseases,national institutes of allergy and infectious diseases,national institutes of health,bethesda,md, United States, laboratory of parasitic diseases,national institutes of allergy and infectious diseases,national institutes of health,bethesda,md, United States, laboratory of parasitic diseases,national institutes of allergy and infectious diseases,national institutes of health,bethesda,md, United States, laboratory of parasitic diseases,national institutes of allergy and infectious diseases,national institutes of health,bethesda,md, United States, laboratory of parasitic diseases,national institutes of allergy and infectious diseases,national institutes of health,bethesda,md, United States
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Authors
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