ArticleNature microbiology2021
Escherichia coli Rho GTPase-activating toxin CNF1 mediates NLRP3 inflammasome activation via p21-activated kinases-1/2 during bacteraemia in mice.
Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Effects of theInternational journal of molecular sciences · 2021Pooled it
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- Sensing the spectrum: diverse stimuli for the NLRP3 inflammasome.Communications biology · 2026Review
- Pyroptosis in cerebral ischemia‑reperfusion injury: Molecular mechanisms and therapeutic implications (Review).Molecular medicine reports · 2026Review
- Post-translational modifications of NLRP3: to prime or not to prime?Trends in immunology · 2026Review
- Deciphering the NEK7-NLRP3 inflammasome assembly: from conformational activation to allosteric drug discovery.Frontiers in immunology · 2026Review
- Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances.Journal of hematology & oncology · 2025Review
- Bacterial infection in weaned piglets promotes diarrhea by inducing the NLRP3 inflammasome-pyroptosis pathway.Science China. Life sciences · 2025Article
- Virulence factors and outcomes in bacteremia caused by extended-spectrum β-lactamase-producing uropathogenic Escherichia coli ST131-H30Rx in a Swedish county.BMC infectious diseases · 2025Article
- NLRP3 inflammasome impairs fracture repair in Rheumatoid arthritis through RhoA/Rac1-IL1β axis-mediated suppression of osteoblast differentiation.Journal of orthopaedic translation · 2025Article
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- Guards and decoys: RIPoptosome and inflammasome pathway regulators of bacterial effector-triggered immunity.PLoS pathogens · 2025Review
- Article
- The regulation of pyroptosis by post-translational modifications: molecular mechanisms and therapeutic targets.EBioMedicine · 2024Review
- RAC2 gain-of-function variants causing inborn error of immunity drive NLRP3 inflammasome activation.The Journal of experimental medicine · 2024Article
- Combined bacterial translocation and cholestasis aggravates liver injury by activation pyroptosis in obstructive jaundice.Heliyon · 2024Article
- Article
- Single-cell analysis identifies conserved features of immune dysfunction in simulated microgravity and spaceflight.Nature communications · 2024Article
- Post-translational control of NLRP3 inflammasome signaling.The Journal of biological chemistry · 2024Review
- Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner.Communications biology · 2024Article
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Authors and funding
22 authors at 5 institutions in 3 countries.
Funding
Abstract
Inflammasomes are signalling platforms that are assembled in response to infection or sterile inflammation by cytosolic pattern recognition receptors. The consequent inflammasome-triggered caspase-1 activation is critical for the host defence against pathogens. During infection, NLRP3, which is a pattern recognition receptor that is also known as cryopyrin, triggers the assembly of the inflammasome-activating caspase-1 through the recruitment of ASC and Nek7. The activation of the NLRP3 inflammasome is tightly controlled both transcriptionally and post-translationally. Despite the importance of the NLRP3 inflammasome regulation in autoinflammatory and infectious diseases, little is known about the mechanism controlling the activation of NLRP3 and the upstream signalling that regulates the NLRP3 inflammasome assembly. We have previously shown that the Rho-GTPase-activating toxin from Escherichia coli cytotoxic necrotizing factor-1 (CNF1) activates caspase-1, but the upstream mechanism is unclear. Here, we provide evidence of the role of the NLRP3 inflammasome in sensing the activity of bacterial toxins and virulence factors that activate host Rho GTPases. We demonstrate that this activation relies on the monitoring of the toxin's activity on the Rho GTPase Rac2. We also show that the NLRP3 inflammasome is activated by a signalling cascade that involves the p21-activated kinases 1 and 2 (Pak1/2) and the Pak1-mediated phosphorylation of Thr 659 of NLRP3, which is necessary for the NLRP3-Nek7 interaction, inflammasome activation and IL-1β cytokine maturation. Furthermore, inhibition of the Pak-NLRP3 axis decreases the bacterial clearance of CNF1-expressing UTI89 E. coli during bacteraemia in mice. Taken together, our results establish that Pak1 and Pak2 are critical regulators of the NLRP3 inflammasome and reveal the role of the Pak-NLRP3 signalling axis in vivo during bacteraemia in mice.
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