ArticleCell host & microbe2024
Paneth cell TNF signaling induces gut bacterial translocation and sepsis.
Article in Cell host & microbe, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Host metabolism shapes the intestinal microbiota: a top-down paradigm of environmental selection pressure.Gut microbes · 2026Review
- From gatekeepers to regenerators: the plasticity of Paneth cells.The EMBO journal · 2026Article
- A portable nanobiosensor with machine learning: enabling multi-cytokines point-of-care testing and early identification of sepsis immunoparalysis.Journal of nanobiotechnology · 2026Article
- Cytokine networks in Paneth cell regulation.Mucosal immunology · 2026Review
- Gut microbiota dysbiosis in sepsis and sepsis-associated organ injury: mechanisms, gut-organ axes, and therapeutic strategies.Frontiers in microbiology · 2026Review
- Neutrophils and NETs in Pathophysiology and Treatment of Inflammatory Bowel Disease.International journal of molecular sciences · 2025Review
- Preoperative TNF-α predicts uneventful postoperative outcomes in patients undergoing colorectal cancer surgery.Scientific reports · 2025Observational
- Immunogenic cell death biomarkers for sepsis diagnosis and mechanism via integrated bioinformatics.Scientific reports · 2025Article
- Sublethal systemic LPS in mice enables gut-luminal pathogens to bloom through oxygen species-mediated microbiota inhibition.Nature communications · 2025Article
- Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanisms conferring multi-layered protection against intestinal Salmonella Typhimurium infection.FEMS microbiology reviews · 2025Review
- Reassessing sepsis research: new clues for old players and new players for an old symptom to improve patient outcomes.EXCLI journal · 2025Review
- The role of α-hydroxybutyrate in modulating sepsis progression: identification of key targets and biomarkers through multi-database data mining, machine learning, and unsupervised clustering.Frontiers in pharmacology · 2025Article
- Mechanisms of sepsis-induced acute liver injury: a comprehensive review.Frontiers in cellular and infection microbiology · 2025Review
- A crucial role of the malate aspartate shuttle in metabolic reprogramming in TNF-induced SIRS.Frontiers in immunology · 2025Article
- Detection of chimeric alpha-defensin transcripts and peptides in mouse Paneth cells.Frontiers in immunology · 2025Article
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19 authors.
Funding
Abstract
The cytokine tumor necrosis factor (TNF) plays important roles in limiting infection but is also linked to sepsis. The mechanisms underlying these paradoxical roles are unclear. Here, we show that TNF limits the antimicrobial activity of Paneth cells (PCs), causing bacterial translocation from the gut to various organs. This TNF-induced lethality does not occur in mice with a PC-specific deletion in the TNF receptor, P55. In PCs, TNF stimulates the IFN pathway and ablates the steady-state unfolded protein response (UPR), effects not observed in mice lacking P55 or IFNAR1. TNF triggers the transcriptional downregulation of IRE1 key genes Ern1 and Ern2, which are key mediators of the UPR. This UPR deficiency causes a significant reduction in antimicrobial peptide production and PC antimicrobial activity, causing bacterial translocation to organs and subsequent polymicrobial sepsis, organ failure, and death. This study highlights the roles of PCs in bacterial control and therapeutic targets for sepsis.
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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.