ArticlePLoS biology2020
Clustering of Tir during enteropathogenic E. coli infection triggers calcium influx-dependent pyroptosis in intestinal epithelial cells.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- EnteropathogeniceLife · 2026Article
- GBP1 recruitment to actin-rich pedestals of extracellular Gram-negative bacteria promotes pyroptosis.The EMBO journal · 2026Article
- Infectious Diarrhea in Early Childhood across the Global South: Etiologic Diversity and Pathogenic Mechanisms.ACS infectious diseases · 2026Review
- GBP1 recruitment to actin-rich pedestals induced by extracellular Gram negative bacteria promotes pyroptosis.bioRxiv : the preprint server for biology · 2025Article
- Macula Densa Alleviates Shiga Toxin-Induced Acute Kidney Injury via CCN1-Mediated Renal Tubular Repair.Toxins · 2025Article
- Sodium Butyrate Inhibits Necroptosis by Regulating MLKL via E2F1 in Intestinal Epithelial Cells of Liver Cirrhosis.Journal of clinical and translational hepatology · 2025Article
- Why put yourself on a pedestal? The pathogenic role of the A/E pedestal.Infection and immunity · 2024Review
- The pathogen-encoded signalling receptor Tir exploits host-like intrinsic disorder for infection.Communications biology · 2024Article
- The role of TRPV4 in programmed cell deaths.Molecular biology reports · 2024Review
- To die or not to die: Gasdermins in intestinal health and disease.Seminars in immunology · 2024Review
- Advances in research on the impact and mechanisms of pathogenic microorganism infections on pyroptosis.Frontiers in microbiology · 2024Review
- Topology and function of translocated EspZ.mBio · 2023Article
- Bacterial toxins and heart function: heat-labileBiophysical reviews · 2023Article
- Yersiniabactin-ProducingInternational journal of molecular sciences · 2023Article
- The gasdermin protein family: emerging roles in gastrointestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2023Review
- The transmembrane domains of the type III secretion system effector Tir are involved in its secretion and cellular activities.Frontiers in cellular and infection microbiology · 2023Article
- Pyroptosis-Induced Inflammation and Tissue Damage.Journal of molecular biology · 2022Review
- Intestinal Gasdermins for regulation of inflammation and tumorigenesis.Frontiers in immunology · 2022Review
- Inflammasome-Induced Osmotic Pressure and the Mechanical Mechanisms Underlying Astrocytic Swelling and Membrane Blebbing in Pyroptosis.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Clustering of the enteropathogenic Escherichia coli (EPEC) type III secretion system (T3SS) effector translocated intimin receptor (Tir) by intimin leads to actin polymerisation and pyroptotic cell death in macrophages. The effect of Tir clustering on the viability of EPEC-infected intestinal epithelial cells (IECs) is unknown. We show that EPEC induces pyroptosis in IECs in a Tir-dependent but actin polymerisation-independent manner, which was enhanced by priming with interferon gamma (IFNγ). Mechanistically, Tir clustering triggers rapid Ca2+ influx, which induces lipopolysaccharide (LPS) internalisation, followed by activation of caspase-4 and pyroptosis. Knockdown of caspase-4 or gasdermin D (GSDMD), translocation of NleF, which blocks caspase-4 or chelation of extracellular Ca2+, inhibited EPEC-induced cell death. IEC lines with low endogenous abundance of GSDMD were resistant to Tir-induced cell death. Conversely, ATP-induced extracellular Ca2+ influx enhanced cell death, which confirmed the key regulatory role of Ca2+ in EPEC-induced pyroptosis. We reveal a novel mechanism through which infection with an extracellular pathogen leads to pyroptosis in IECs.
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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.