ArticleThe Journal of experimental medicine2023
EEF2-inactivating toxins engage the NLRP1 inflammasome and promote epithelial barrier disruption.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 35 citations in OpenAlex.
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- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- Antiviral Inflammasomes and How to Find Them.Viruses · 2026Review
- TAK1 integrates the NLRP1 inflammasome into the innate immune response to double-stranded RNA.bioRxiv : the preprint server for biology · 2026Article
- Redefining Shiga toxin-induced human cell death as NLRP1- and gasdermin E-mediated pyroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Intrinsically disordered regions in the NLRP family of receptors act as regulatory hubs for inflammasome condensation and activation.Frontiers in immunology · 2026Article
- Sibiriline, a novel dual inhibitor of necroptosis and ferroptosis, prevents RIPK1 kinase activity and (phospho)lipid peroxidation as a potential therapeutic strategy.Cell death discovery · 2025Article
- Impact of NLRP1 Met1154Val and IL1B variants on gestational malaria: an unexplored role of NLRP1 in inflammasome activation by Plasmodium spp.The Journal of pathology · 2025Article
- Discovery of papyifuran A as an unusual cembrane diterpenoid fromActa pharmaceutica Sinica. B · 2025Article
- Antibacterial Activity of the p53 Tumor Suppressor Protein-How Strong Is the Evidence?International journal of molecular sciences · 2025Review
- A viral E3 ubiquitin ligase produced by herpes simplex virus 1 inhibits the NLRP1 inflammasome.The Journal of experimental medicine · 2024Article
- A viral E3 ubiquitin ligase produced by herpes simplex virus 1 inhibits the NLRP1 inflammasome.The Journal of experimental medicine · 2024Article
- Strategies of bacterial detection by inflammasomes.Cell chemical biology · 2024Review
- PemB, a type III secretion effector inHeliyon · 2024Article
- Mechanistic basis for potassium efflux-driven activation of the human NLRP1 inflammasome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- NLRP1- A CINDERELLA STORY: a perspective of recent advances in NLRP1 and the questions they raise.Communications biology · 2023Review
- Diphtheria toxin activates ribotoxic stress and NLRP1 inflammasome-driven pyroptosis.The Journal of experimental medicine · 2023Article
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22 authors at 5 institutions in 2 countries.
Funding
Abstract
Human airway and corneal epithelial cells, which are critically altered during chronic infections mediated by Pseudomonas aeruginosa, specifically express the inflammasome sensor NLRP1. Here, together with a companion study, we report that the NLRP1 inflammasome detects exotoxin A (EXOA), a ribotoxin released by P. aeruginosa type 2 secretion system (T2SS), during chronic infection. Mechanistically, EXOA-driven eukaryotic elongation factor 2 (EEF2) ribosylation and covalent inactivation promote ribotoxic stress and subsequent NLRP1 inflammasome activation, a process shared with other EEF2-inactivating toxins, diphtheria toxin and cholix toxin. Biochemically, irreversible EEF2 inactivation triggers ribosome stress-associated kinases ZAKα- and P38-dependent NLRP1 phosphorylation and subsequent proteasome-driven functional degradation. Finally, cystic fibrosis cells from patients exhibit exacerbated P38 activity and hypersensitivity to EXOA-induced ribotoxic stress-dependent NLRP1 inflammasome activation, a process inhibited by the use of ZAKα inhibitors. Altogether, our results show the importance of P. aeruginosa virulence factor EXOA at promoting NLRP1-dependent epithelial damage and identify ZAKα as a critical sensor of virulence-inactivated EEF2.
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