Cargando…

DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway

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 me...

Descripción completa

Detalles Bibliográficos
Autores principales: Tsai, Su-Yu, Segovia, Jesus A., Chang, Te-Hung, Morris, Ian R., Berton, Michael T., Tessier, Philippe A., Tardif, Mélanie R., Cesaro, Annabelle, Bose, Santanu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879357/
https://www.ncbi.nlm.nih.gov/pubmed/24391503
http://dx.doi.org/10.1371/journal.ppat.1003848
_version_ 1782297969601544192
author Tsai, Su-Yu
Segovia, Jesus A.
Chang, Te-Hung
Morris, Ian R.
Berton, Michael T.
Tessier, Philippe A.
Tardif, Mélanie R.
Cesaro, Annabelle
Bose, Santanu
author_facet Tsai, Su-Yu
Segovia, Jesus A.
Chang, Te-Hung
Morris, Ian R.
Berton, Michael T.
Tessier, Philippe A.
Tardif, Mélanie R.
Cesaro, Annabelle
Bose, Santanu
author_sort Tsai, Su-Yu
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3879357
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-38793572014-01-03 DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway Tsai, Su-Yu Segovia, Jesus A. Chang, Te-Hung Morris, Ian R. Berton, Michael T. Tessier, Philippe A. Tardif, Mélanie R. Cesaro, Annabelle Bose, Santanu PLoS Pathog Research Article 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. Public Library of Science 2014-01-02 /pmc/articles/PMC3879357/ /pubmed/24391503 http://dx.doi.org/10.1371/journal.ppat.1003848 Text en © 2014 Tsai et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tsai, Su-Yu
Segovia, Jesus A.
Chang, Te-Hung
Morris, Ian R.
Berton, Michael T.
Tessier, Philippe A.
Tardif, Mélanie R.
Cesaro, Annabelle
Bose, Santanu
DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway
title DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway
title_full DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway
title_fullStr DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway
title_full_unstemmed DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway
title_short DAMP Molecule S100A9 Acts as a Molecular Pattern to Enhance Inflammation during Influenza A Virus Infection: Role of DDX21-TRIF-TLR4-MyD88 Pathway
title_sort damp molecule s100a9 acts as a molecular pattern to enhance inflammation during influenza a virus infection: role of ddx21-trif-tlr4-myd88 pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879357/
https://www.ncbi.nlm.nih.gov/pubmed/24391503
http://dx.doi.org/10.1371/journal.ppat.1003848
work_keys_str_mv AT tsaisuyu dampmolecules100a9actsasamolecularpatterntoenhanceinflammationduringinfluenzaavirusinfectionroleofddx21triftlr4myd88pathway
AT segoviajesusa dampmolecules100a9actsasamolecularpatterntoenhanceinflammationduringinfluenzaavirusinfectionroleofddx21triftlr4myd88pathway
AT changtehung dampmolecules100a9actsasamolecularpatterntoenhanceinflammationduringinfluenzaavirusinfectionroleofddx21triftlr4myd88pathway
AT morrisianr dampmolecules100a9actsasamolecularpatterntoenhanceinflammationduringinfluenzaavirusinfectionroleofddx21triftlr4myd88pathway
AT bertonmichaelt dampmolecules100a9actsasamolecularpatterntoenhanceinflammationduringinfluenzaavirusinfectionroleofddx21triftlr4myd88pathway
AT tessierphilippea dampmolecules100a9actsasamolecularpatterntoenhanceinflammationduringinfluenzaavirusinfectionroleofddx21triftlr4myd88pathway
AT tardifmelanier dampmolecules100a9actsasamolecularpatterntoenhanceinflammationduringinfluenzaavirusinfectionroleofddx21triftlr4myd88pathway
AT cesaroannabelle dampmolecules100a9actsasamolecularpatterntoenhanceinflammationduringinfluenzaavirusinfectionroleofddx21triftlr4myd88pathway
AT bosesantanu dampmolecules100a9actsasamolecularpatterntoenhanceinflammationduringinfluenzaavirusinfectionroleofddx21triftlr4myd88pathway