ArticleThe Journal of experimental medicine2023
Diphtheria toxin activates ribotoxic stress and NLRP1 inflammasome-driven pyroptosis.
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 36 papers.
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Who cites it
36 citing papers in PubMed, 50 citations in OpenAlex.
- Multimodality Molecular Profiling Nominates Targetable Mechanisms in Progressive RV Dysfunction.Circulation research · 2026Article
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.The Journal of clinical investigation · 2026Article
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.The Journal of clinical investigation · 2026Article
- Mechanisms and therapeutic opportunities of the ribotoxic stress response in cancer.Molecular oncology · 2026Review
- Reverse genetics in humanized mice reveals CARD8-mediated pyroptosis causing pancytopenia in human DPP9 deficiency.bioRxiv : the preprint server for biology · 2026Article
- NLRP1 promotes pyroptosis in endometriosis through the NF-κB signaling pathway.Scientific reports · 2026Article
- Lethal toxin-equipped effector cells for the potential treatment of cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multimodality Molecular Profiling Nominates Targetable Mechanisms in Progressive RV Dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Antiviral Inflammasomes and How to Find Them.Viruses · 2026Review
- 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
- Mechanoresponsive reprogramming of tumor-associated macrophages during cancer progression.Frontiers in cell and developmental biology · 2026Review
- Secondary Necrosis Following Caspase-Activation can Occur Independently of Gasdermin E.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Descendants of hypertrophic chondrocytes promote angiogenesis by secreting THBS4 during bone growth and injury repair.Bone research · 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
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- The protective role of adipogenic lineage precursors in maintaining bone marrow redox homeostasis in a mouse model of prenatal dexamethasone exposure.Redox biology · 2025Article
- ZAKα Induces Pyroptosis of Colonic Epithelium Via the Caspase-11/GSDMD Pathway to Aggravate Colitis.Inflammation · 2025Article
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14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ZAKα-driven ribotoxic stress response (RSR) is activated by ribosome stalling and/or collisions. Recent work demonstrates that RSR also plays a role in innate immunity by activating the human NLRP1 inflammasome. Here, we report that ZAKα and NLRP1 sense bacterial exotoxins that target ribosome elongation factors. One such toxin, diphtheria toxin (DT), the causative agent for human diphtheria, triggers RSR-dependent inflammasome activation in primary human keratinocytes. This process requires iron-mediated DT production in the bacteria, as well as diphthamide synthesis and ZAKα/p38-driven NLRP1 phosphorylation in host cells. NLRP1 deletion abrogates IL-1β and IL-18 secretion by DT-intoxicated keratinocytes, while ZAKα deletion or inhibition additionally limits both pyroptotic and inflammasome-independent non-pyroptotic cell death. Consequently, pharmacologic inhibition of ZAKα is more effective than caspase-1 inhibition at protecting the epidermal barrier in a 3D skin model of cutaneous diphtheria. In summary, these findings implicate ZAKα-driven RSR and the NLRP1 inflammasome in antibacterial immunity and might explain certain aspects of diphtheria pathogenesis.
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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.