ArticleNature2014
Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 490 papers, 1 of them a synthesis that pooled it.
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Who cites it
490 citing papers in PubMed, 1 synthesis or guideline pooled it, 814 citations in OpenAlex.
- Interventions for reducing inflammation in familial Mediterranean fever.The Cochrane database of systematic reviews · 2022Pooled it
- WNK1 links ionic signals to microtubule dynamics to control pyrin inflammasome assembly.Science advances · 2026Article
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Innate immune sensors of inflammasomes and PANoptosomes: structural-mechanistic insights and therapeutic implications.Cell research · 2026Review
- Advancements in Diagnosis and Care for Immune Dysregulation and Inborn Errors of Immunity in Pediatric Rheumatology: Our 50-Year Journey.Arthritis care & research · 2026Review
- Malvidin-3-O-Rhamnoside Alleviates Klebsiella pneumoniae -Induced Acute Lung Injury by Regulating Macrophage-Mediated Inflammatory and Oxidative Pathways.Phytotherapy research : PTR · 2026Article
- Mechanisms and therapeutic strategies of pyroptosis in sepsis‑induced acute lung injury (Review).International journal of molecular medicine · 2026Review
- Balancing act of cytokines in controlling the severity ofInfection and immunity · 2026Review
- Clinical spectrum of pediatric patients carrying heterozygous MEFV gene variants.European journal of pediatrics · 2026Article
- Cell-autonomous immunity as an integrated immune network against bacterial and viral pathogens.Nature microbiology · 2026Review
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- Pyroptosis: Molecular mechanisms and function.Journal of physiology and biochemistry · 2026Review
- Opsonization Improves Dual Proteomic Analysis ofJournal of proteome research · 2026Article
- Dual activation of NLRP3 and pyrin inflammasomes mediates host responses to the human fungal pathogen Coccidioides.Nature communications · 2026Article
- Threat assessment shapes neutrophil cell fate upon inflammasome activation.Science advances · 2026Article
- MAP4Ks drive cell death in response tomBio · 2026Article
- ThebioRxiv : the preprint server for biology · 2026Article
- Pharmacological targeting of the NLRP3 LRR domain with isothiazolinones overcomes CRID3-resistant inflammation.EMBO molecular medicine · 2026Article
- Sensing the spectrum: diverse stimuli for the NLRP3 inflammasome.Communications biology · 2026Review
- Article
430 more citing papers are in PubMed but not listed here.
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12 authors at 3 institutions in 1 country.
Funding
Abstract
Cytosolic inflammasome complexes mediated by a pattern recognition receptor (PRR) defend against pathogen infection by activating caspase 1. Pyrin, a candidate PRR, can bind to the inflammasome adaptor ASC to form a caspase 1-activating complex. Mutations in the Pyrin-encoding gene, MEFV, cause a human autoinflammatory disease known as familial Mediterranean fever. Despite important roles in immunity and disease, the physiological function of Pyrin remains unknown. Here we show that Pyrin mediates caspase 1 inflammasome activation in response to Rho-glucosylation activity of cytotoxin TcdB, a major virulence factor of Clostridium difficile, which causes most cases of nosocomial diarrhoea. The glucosyltransferase-inactive TcdB mutant loses the inflammasome-stimulating activity. Other Rho-inactivating toxins, including FIC-domain adenylyltransferases (Vibrio parahaemolyticus VopS and Histophilus somni IbpA) and Clostridium botulinum ADP-ribosylating C3 toxin, can also biochemically activate the Pyrin inflammasome in their enzymatic activity-dependent manner. These toxins all target the Rho subfamily and modify a switch-I residue. We further demonstrate that Burkholderia cenocepacia inactivates RHOA by deamidating Asn 41, also in the switch-I region, and thereby triggers Pyrin inflammasome activation, both of which require the bacterial type VI secretion system (T6SS). Loss of the Pyrin inflammasome causes elevated intra-macrophage growth of B. cenocepacia and diminished lung inflammation in mice. Thus, Pyrin functions to sense pathogen modification and inactivation of Rho GTPases, representing a new paradigm in mammalian innate immunity.
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Registered trials
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.