Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome.
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 act...
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Public Library of Science (PLoS)
2012
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oai:doaj.org-article:92d7ede8a47440739881cd70d2f2c59a2021-11-18T06:04:36ZAnthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome.1553-73661553-737410.1371/journal.ppat.1002638https://doaj.org/article/92d7ede8a47440739881cd70d2f2c59a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22479187/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374NOD-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.Jonathan L LevinsohnZachary L NewmanKristina A HellmichRasem FattahMatthew A GetzShihui LiuInka SastallaStephen H LepplaMahtab MoayeriPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 3, p e1002638 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jonathan L Levinsohn Zachary L Newman Kristina A Hellmich Rasem Fattah Matthew A Getz Shihui Liu Inka Sastalla Stephen H Leppla Mahtab Moayeri Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. |
| description |
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. |
| format |
article |
| author |
Jonathan L Levinsohn Zachary L Newman Kristina A Hellmich Rasem Fattah Matthew A Getz Shihui Liu Inka Sastalla Stephen H Leppla Mahtab Moayeri |
| author_facet |
Jonathan L Levinsohn Zachary L Newman Kristina A Hellmich Rasem Fattah Matthew A Getz Shihui Liu Inka Sastalla Stephen H Leppla Mahtab Moayeri |
| author_sort |
Jonathan L Levinsohn |
| title |
Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. |
| title_short |
Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. |
| title_full |
Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. |
| title_fullStr |
Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. |
| title_full_unstemmed |
Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. |
| title_sort |
anthrax lethal factor cleavage of nlrp1 is required for activation of the inflammasome. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/92d7ede8a47440739881cd70d2f2c59a |
| work_keys_str_mv |
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1718424617754820608 |