ArticlePLoS pathogens2014
DAMP molecule S100A9 acts as a molecular pattern to enhance inflammation during influenza A virus infection: role of DDX21-TRIF-TLR4-MyD88 pathway.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 197 citations in OpenAlex.
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- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Systems-Level Analysis of HPAI H5N1 Infection in Ducks: Integrating Transcriptomic, Proteomic, and Phosphoproteomic Data.International journal of molecular sciences · 2026Article
- Update on the Efficacy of Vaccination on Host Immunity to Influenza Virus Infection.International archives of allergy and immunology · 2026Review
- Targeting S100A8/A9: a molecular gateway to oral inflammation, microglial activation and neuroinflammation.Frontiers in immunology · 2026Review
- Reading of human acute immune dynamics in omicron SARS-CoV-2 breakthrough infection.Emerging microbes & infections · 2025Article
- Thioredoxin regulates T cell proliferation and aggravates the severity of influenza a virus infection.Scientific reports · 2025Article
- Role of DEAD/DEAH-box helicases in immunity, infection and cancers.Cell communication and signaling : CCS · 2025Review
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- Established and Emerging Roles of DEAD/H-Box Helicases in Regulating Infection and Immunity.Immunological reviews · 2025Review
- S100A8/A9 in herpes zoster neuralgia: molecular mechanisms and therapeutic perspectives.Frontiers in immunology · 2025Review
- DDX21 at the Nexus of RNA Metabolism, Cancer Oncogenesis, and Host-Virus Crosstalk: Decoding Its Biomarker Potential and Therapeutic Implications.International journal of molecular sciences · 2024Review
- Novel Long Noncoding RNACirculation · 2024Article
- Effect of Mixed Probiotics on Alleviating H1N1 Influenza Infection and Regulating Gut Microbiota.Foods (Basel, Switzerland) · 2024Article
- scPanel: a tool for automatic identification of sparse gene panels for generalizable patient classification using scRNA-seq datasets.Briefings in bioinformatics · 2024Article
- Saffron as a Promising Therapy for Inflammatory Bowel Disease.Nutrients · 2024Review
- Data-independent LC-MS/MS analysis of ME/CFS plasma reveals a dysregulated coagulation system, endothelial dysfunction, downregulation of complement machinery.Cardiovascular diabetology · 2024Article
- Review
- Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape.Pathogens (Basel, Switzerland) · 2024Review
67 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Pathogen-associated molecular patterns (PAMPs) trigger host immune response by activating pattern recognition receptors like toll-like receptors (TLRs). However, the mechanism whereby several pathogens, including viruses, activate TLRs via a non-PAMP mechanism is unclear. Endogenous "inflammatory mediators" called damage-associated molecular patterns (DAMPs) have been implicated in regulating immune response and inflammation. However, the role of DAMPs in inflammation/immunity during virus infection has not been studied. We have identified a DAMP molecule, S100A9 (also known as Calgranulin B or MRP-14), as an endogenous non-PAMP activator of TLR signaling during influenza A virus (IAV) infection. S100A9 was released from undamaged IAV-infected cells and extracellular S100A9 acted as a critical host-derived molecular pattern to regulate inflammatory response outcome and disease during infection by exaggerating pro-inflammatory response, cell-death and virus pathogenesis. Genetic studies showed that the DDX21-TRIF signaling pathway is required for S100A9 gene expression/production during infection. Furthermore, the inflammatory activity of extracellular S100A9 was mediated by activation of the TLR4-MyD88 pathway. Our studies have thus, underscored the role of a DAMP molecule (i.e. extracellular S100A9) in regulating virus-associated inflammation and uncovered a previously unknown function of the DDX21-TRIF-S100A9-TLR4-MyD88 signaling network in regulating inflammation during infection.
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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.