title: TLR7 contributes to the rapid progression but not to the overall fatal outcome of secondary pneumococcal disease following influenza A virus infection.
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.
authors.affiliation: Immune Regulation Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Stegemann-Koniszewski
authors.forename: Marcus
authors.initials: M
authors.lastname: Gereke
authors.forename: Sofia
authors.initials: S
authors.lastname: Orrskog
authors.forename: Stefan
authors.initials: S
authors.lastname: Lienenklaus
authors.forename: Bastian
authors.initials: B
authors.lastname: Pasche
authors.forename: Sophie R
authors.initials: SR
authors.lastname: Bader
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.forename: Birgitta
authors.initials: B
authors.lastname: Henriques-Normark
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
authors.forename: Matthias
authors.initials: M
authors.lastname: Gunzer
mesh_terms: D000818:Animals; D018450:Disease Progression; D004285:Dogs; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications / Q000276:immunology*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000235:genetics; D011008:Pneumococcal Infections / Q000150:complications / Q000276:immunology*; D015163:Superinfection / Q000150:complications / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D016899:Interferon-beta