ArticlePLoS pathogens2013
Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed, 236 citations in OpenAlex.
- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- IFN-α and IFN-β inhibit NLRP1-driven PANoptosis.EMBO reports · 2026Article
- Article
- Structure of the E3 ligase CRL2Cell reports · 2026Article
- NLRP1B is an integrated decoy that subvertsProceedings of the National Academy of Sciences of the United States of America · 2026Article
- TAK1 integrates the NLRP1 inflammasome into the innate immune response to double-stranded RNA.bioRxiv : the preprint server for biology · 2026Article
- Pyroptosis of Vascular Smooth Muscle Cells as a Potential New Target for Preventing Vascular Diseases.Cardiovascular drugs and therapy · 2025Review
- A comprehensive analysis of the relationship between inflammasomes and autophagy in human tumors: Recent developments.Journal of cell communication and signaling · 2025Review
- Targeting innate immune sensors for therapeutic strategies in infectious diseases.Journal of microbiology (Seoul, Korea) · 2025Review
- Review
- Diverse autoinhibitory mechanisms of FIIND-containing proteins: Insight into regulation of NLRP1 and CARD8 inflammasome.PLoS pathogens · 2025Article
- Guards and decoys: RIPoptosome and inflammasome pathway regulators of bacterial effector-triggered immunity.PLoS pathogens · 2025Review
- The role of pyroptosis in cancer: key components and therapeutic potential.Cell communication and signaling : CCS · 2024Review
- NLRP1-dependent activation of Gasdermin D in neutrophils controls cutaneous leishmaniasis.PLoS pathogens · 2024Article
- ER-transiting bacterial toxins amplify STING innate immune responses and elicit ER stress.Infection and immunity · 2024Article
- Mechanistic insights from inflammasome structures.Nature reviews. Immunology · 2024Review
- Conservation and similarity of bacterial and eukaryotic innate immunity.Nature reviews. Microbiology · 2024Review
- Strategies of bacterial detection by inflammasomes.Cell chemical biology · 2024Review
- The NLR family of innate immune and cell death sensors.Immunity · 2024Review
- The interaction of inflammasomes and gut microbiota: novel therapeutic insights.Cell communication and signaling : CCS · 2024Review
82 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
Inflammasomes are multimeric protein complexes that respond to infection by recruitment and activation of the Caspase-1 (CASP1) protease. Activated CASP1 initiates immune defense by processing inflammatory cytokines and by causing a rapid and lytic cell death called pyroptosis. Inflammasome formation is orchestrated by members of the nucleotide-binding domain and leucine-rich repeat (NLR) or AIM2-like receptor (ALR) protein families. Certain NLRs and ALRs have been shown to function as direct receptors for specific microbial ligands, such as flagellin or DNA, but the molecular mechanism responsible for activation of most NLRs is still poorly understood. Here we determine the mechanism of activation of the NLRP1B inflammasome in mice. NLRP1B, and its ortholog in rats, is activated by the lethal factor (LF) protease that is a key virulence factor secreted by Bacillus anthracis, the causative agent of anthrax. LF was recently shown to cleave mouse and rat NLRP1 directly. However, it is unclear if cleavage is sufficient for NLRP1 activation. Indeed, other LF-induced cellular events have been suggested to play a role in NLRP1B activation. Surprisingly, we show that direct cleavage of NLRP1B is sufficient to induce inflammasome activation in the absence of LF. Our results therefore rule out the need for other LF-dependent cellular effects in activation of NLRP1B. We therefore propose that NLRP1 functions primarily as a sensor of protease activity and thus could conceivably detect a broader spectrum of pathogens than just B. anthracis. By adding proteolytic cleavage to the previously established ligand-receptor mechanism of NLR activation, our results illustrate the remarkable flexibility with which the NLR architecture can be deployed for the purpose of pathogen-detection and host defense.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.