Journal article
DAMP molecule S100A9 acts as a molecular pattern to enhance inflammation during influenza A virus infection: role of DDX21-TRIF-TLR4-MyD88 pathway
PLoS pathogens, Vol.10(1), pp.e1003848-e1003848
01/2014
Handle:
https://hdl.handle.net/2376/109830
PMCID: PMC3879357
PMID: 24391503
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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Details
- Title
- DAMP molecule S100A9 acts as a molecular pattern to enhance inflammation during influenza A virus infection: role of DDX21-TRIF-TLR4-MyD88 pathway
- Creators
- Su-Yu Tsai - Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of AmericaJesus A Segovia - Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of AmericaTe-Hung Chang - Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of AmericaIan R Morris - Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of AmericaMichael T Berton - Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of AmericaPhilippe A Tessier - Axe Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec, and Faculté de Médecine, Université Laval, Quebec, CanadaMélanie R Tardif - Axe Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec, and Faculté de Médecine, Université Laval, Quebec, CanadaAnnabelle Cesaro - Axe Maladies Infectieuses et Immunitaires, Centre de Recherche du CHU de Québec, and Faculté de Médecine, Université Laval, Quebec, CanadaSantanu Bose - Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America
- Publication Details
- PLoS pathogens, Vol.10(1), pp.e1003848-e1003848
- Academic Unit
- Veterinary Microbiology and Pathology, Department of
- Publisher
- United States
- Grant note
- UL1 TR001120 / NCATS NIH HHS DE14318 / NIDCR NIH HHS R01 AI083387 / NIAID NIH HHS AI057986 / NIAID NIH HHS P01 AI057986 / NIAID NIH HHS T32 DE014318 / NIDCR NIH HHS 84226 / Canadian Institutes of Health Research KL2 TR001118 / NCATS NIH HHS 8UL1 TR000149. / NCATS NIH HHS UL1 TR000149 / NCATS NIH HHS AI083387 / NIAID NIH HHS
- Identifiers
- 99900547020401842
- Language
- English
- Resource Type
- Journal article