Journal
ANNUAL REVIEW OF IMMUNOLOGY, VOL 31
Volume 31, Issue -, Pages 73-106Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-immunol-032712-095944
Keywords
caspase; NLR; innate immunity; pyroptosis
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Funding
- Cancer Research Institute
- Burroughs Wellcome Fund
- University of California Cancer Research Coordinating Committee
- National Science Foundation Graduate Research Fellowship
- National Institutes of Health Ruth L. Kirschstein National Research Service Award Fellowship [AI091068]
- National Institutes of Health R01 grants [AI063302, AI075039, AI080749]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI075039, R01AI080749] Funding Source: NIH RePORTER
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Inflammasomes are cytosolic multiprotein complexes that assemble in response to a variety of infectious and noxious insults. Inflammasomes play a critical role in the initiation of innate immune responses, primarily by serving as platforms for the activation of inflammatory caspase proteases. One such caspase, CASPASE-1 (CASP1), initiates innate immune responses by cleaving pro-IL-1 beta and pro-IL-18, leading to their activation and release. CASP1 and another inflammatory caspase termed CASP11 can also initiate a rapid and inflammatory form of cell death termed pyroptosis. Several distinct inflammasomes have been described, each of which contains a unique sensor protein of the NLR (nucleotide-binding domain, leucine-rich repeat-containing) superfamily or the PYHIN (PYRIN and HIN-200 domain-containing) superfamily. Here we describe the surprisingly diverse mechanisms by which NLR/PYHIN proteins sense bacteria and initiate innate immune responses. We conclude that inflammasomes represent a highly adaptable scaffold ideally suited for detecting and initiating rapid innate responses to diverse and rapidly evolving bacteria.
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