ArticleCell death and differentiation2017
Pore-forming toxin-mediated ion dysregulation leads to death receptor-independent necroptosis of lung epithelial cells during bacterial pneumonia.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
71 citing papers in PubMed, 107 citations in OpenAlex.
- Phage-Antibiotic-Peptide Synergy Overcomes Biofilm-Mediated Multidrug Resistance inAntibiotics (Basel, Switzerland) · 2026Article
- Alveolar epithelial barrier disruption by FKBP5-mediated necroptosis aggravates lung injury.Respiratory research · 2026Article
- A Triple-Modality Peptide-Antibiotic-Phage Therapy Eradicates Multidrug-ResistantbioRxiv : the preprint server for biology · 2026Article
- Basement membranes in lung development, disease, and repair.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
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- Vibrio cholerae cytolysin induces pro-inflammatory and death signals through novel TLR assembly.PLoS pathogens · 2025Article
- Targeting PANoptosis in Bacterial-Induced Inflammatory Diseases: Mechanisms and Therapeutic Interventions.Journal of inflammation research · 2025Review
- Regulated programmed cell death in acute lung injury: from pathogenesis to therapy.Frontiers in immunology · 2025Review
- Blocking HXAmBio · 2024Article
- Targeting necroptosis: a promising avenue for respiratory disease treatment.Cell communication and signaling : CCS · 2024Review
- Blocking HXAbioRxiv : the preprint server for biology · 2024Article
- Story of Pore-Forming Proteins from Deadly Disease-Causing Agents to Modern Applications with Evolutionary Significance.Molecular biotechnology · 2024Review
- Membrane Dynamics and Cation Handling in Ferroptosis.Physiology (Bethesda, Md.) · 2024Review
- Review
- Mitochondrial Reactive Oxygen Species and Lytic Programmed Cell Death in Acute Inflammation.Antioxidants & redox signaling · 2023Review
- The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy.International journal of molecular sciences · 2023Review
- Acute organ injury and long-term sequelae of severe pneumococcal infections.Pneumonia (Nathan Qld.) · 2023Review
- An Atypical, Staged Cell Death Pathway Induced by Depletion of SNARE-Proteins MUNC18-1 or Syntaxin-1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- A programmed cell death-related model based on machine learning for predicting prognosis and immunotherapy responses in patients with lung adenocarcinoma.Frontiers in immunology · 2023Article
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
We report that pore-forming toxins (PFTs) induce respiratory epithelial cell necroptosis independently of death receptor signaling during bacterial pneumonia. Instead, necroptosis was activated as a result of ion dysregulation arising from membrane permeabilization. PFT-induced necroptosis required RIP1, RIP3 and MLKL, and could be induced in the absence or inhibition of TNFR1, TNFR2 and TLR4 signaling. We detected activated MLKL in the lungs from mice and nonhuman primates experiencing Serratia marcescens and Streptococcus pneumoniae pneumonia, respectively. We subsequently identified calcium influx and potassium efflux as the key initiating signals responsible for necroptosis; also that mitochondrial damage was not required for necroptosis activation but was exacerbated by MLKL activation. PFT-induced necroptosis in respiratory epithelial cells did not involve CamKII or reactive oxygen species. KO mice deficient in MLKL or RIP3 had increased survival and reduced pulmonary injury during S. marcescens pneumonia. Our results establish necroptosis as a major cell death pathway active during bacterial pneumonia and that necroptosis can occur without death receptor signaling.
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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.