TLR7 contributes to the rapid progression but not to the overall fatal outcome of secondary pneumococcal disease following influenza A virus infection.

2.50
Hdl Handle:
http://hdl.handle.net/10033/298075
Title:
TLR7 contributes to the rapid progression but not to the overall fatal outcome of secondary pneumococcal disease following influenza A virus infection.
Authors:
Stegemann-Koniszewski, Sabine; Gereke, Marcus; Orrskog, Sofia; Lienenklaus, Stefan; Pasche, Bastian; Bader, Sophie R; Gruber, Achim D; Akira, Shizuo; Weiss, Siegfried; Henriques-Normark, Birgitta; Bruder, Dunja ( 0000-0003-3066-189X ) ; Gunzer, Matthias
Abstract:
Increased risk for bacterial superinfections substantially contributes to the mortality caused by influenza A virus (IAV) epidemics. While the mechanistic basis for this lethal synergism is still insufficiently understood, immune modulation through the viral infection has been shown to be involved. Since the pattern-recognition receptor (PRR) toll-like receptor 7 (TLR7) is a major sensor for the viral genome, we studied how IAV recognition by TLR7 influences the development of secondary pneumococcal infection. In a mouse model of IAV, TLR7-deficient hosts induced a potent antiviral response and showed unchanged survival. In secondary pneumococcal infection during acute influenza, TLR7ko mice showed a fatal outcome similar to wild-type (WT) hosts, despite significantly delayed disease progression. Also, when bacterial superinfection occurred after virus clearance, WT and TLR7-deficient hosts showed similar mortality, even though we found the phagocytic activity of alveolar macrophages isolated from IAV-pre-infected hosts to be enhanced in TLR7ko over WT mice. Thus, we show that a virus-sensing PRR modulates the progression of secondary pneumococcal infection following IAV. However, the fatal overall outcome in WT as well as TLR7ko hosts suggests that processes distinct from TLR7-triggering override the contribution of this single PRR.
Affiliation:
Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Citation:
TLR7 contributes to the rapid progression but not to the overall fatal outcome of secondary pneumococcal disease following influenza A virus infection. 2013, 5 (1):84-96 J Innate Immun
Journal:
Journal of innate immunity
Issue Date:
2013
URI:
http://hdl.handle.net/10033/298075
DOI:
10.1159/000345112
PubMed ID:
23154432
Type:
Article
Language:
en
ISSN:
1662-8128
Appears in Collections:
publications of the research group immunoregulation (IREG)

Full metadata record

DC FieldValue Language
dc.contributor.authorStegemann-Koniszewski, Sabineen_GB
dc.contributor.authorGereke, Marcusen_GB
dc.contributor.authorOrrskog, Sofiaen_GB
dc.contributor.authorLienenklaus, Stefanen_GB
dc.contributor.authorPasche, Bastianen_GB
dc.contributor.authorBader, Sophie Ren_GB
dc.contributor.authorGruber, Achim Den_GB
dc.contributor.authorAkira, Shizuoen_GB
dc.contributor.authorWeiss, Siegfrieden_GB
dc.contributor.authorHenriques-Normark, Birgittaen_GB
dc.contributor.authorBruder, Dunjaen_GB
dc.contributor.authorGunzer, Matthiasen_GB
dc.date.accessioned2013-08-13T13:03:50Z-
dc.date.available2013-08-13T13:03:50Z-
dc.date.issued2013-
dc.identifier.citationTLR7 contributes to the rapid progression but not to the overall fatal outcome of secondary pneumococcal disease following influenza A virus infection. 2013, 5 (1):84-96 J Innate Immunen_GB
dc.identifier.issn1662-8128-
dc.identifier.pmid23154432-
dc.identifier.doi10.1159/000345112-
dc.identifier.urihttp://hdl.handle.net/10033/298075-
dc.description.abstractIncreased risk for bacterial superinfections substantially contributes to the mortality caused by influenza A virus (IAV) epidemics. While the mechanistic basis for this lethal synergism is still insufficiently understood, immune modulation through the viral infection has been shown to be involved. Since the pattern-recognition receptor (PRR) toll-like receptor 7 (TLR7) is a major sensor for the viral genome, we studied how IAV recognition by TLR7 influences the development of secondary pneumococcal infection. In a mouse model of IAV, TLR7-deficient hosts induced a potent antiviral response and showed unchanged survival. In secondary pneumococcal infection during acute influenza, TLR7ko mice showed a fatal outcome similar to wild-type (WT) hosts, despite significantly delayed disease progression. Also, when bacterial superinfection occurred after virus clearance, WT and TLR7-deficient hosts showed similar mortality, even though we found the phagocytic activity of alveolar macrophages isolated from IAV-pre-infected hosts to be enhanced in TLR7ko over WT mice. Thus, we show that a virus-sensing PRR modulates the progression of secondary pneumococcal infection following IAV. However, the fatal overall outcome in WT as well as TLR7ko hosts suggests that processes distinct from TLR7-triggering override the contribution of this single PRR.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Journal of innate immunityen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshDisease Progressionen_GB
dc.subject.meshDogsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInfluenza A virusen_GB
dc.subject.meshInfluenza, Humanen_GB
dc.subject.meshInterferon-betaen_GB
dc.subject.meshMadin Darby Canine Kidney Cellsen_GB
dc.subject.meshMembrane Glycoproteinsen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred C57BLen_GB
dc.subject.meshMice, Knockouten_GB
dc.subject.meshPhagocytosisen_GB
dc.subject.meshPneumococcal Infectionsen_GB
dc.subject.meshSuperinfectionen_GB
dc.subject.meshToll-Like Receptor 7en_GB
dc.titleTLR7 contributes to the rapid progression but not to the overall fatal outcome of secondary pneumococcal disease following influenza A virus infection.en
dc.typeArticleen
dc.contributor.departmentImmune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.en_GB
dc.identifier.journalJournal of innate immunityen_GB

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