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TLR7 Contributes to the Rapid Progression but Not to the Overall Fatal Outcome of Secondary Pneumococcal Disease following Influenza A Virus Infection
Sabine Stegemann-Koniszewskia, d, Marcus Gerekea, e, Sofia Orrskogg, Stefan Lienenklausb, Bastian Paschec, Sophie R. Baderf, Achim D. Gruberf, Shizuo Akirah, Siegfried Weissb, Birgitta Henriques-Normarkg, Dunja Brudera, e, Matthias Gunzerd
aImmune Regulation Group,
bMolecular Immunology and
cInfection Genetics, Helmholtz Centre for Infection Research, Braunschweig,
dInstitute of Experimental Immunology and Imaging, University Clinic, University of Duisburg-Essen, Essen,
eInfection Immunology Group, Department of Medical Microbiology, Otto von Guericke University Magdeburg, Magdeburg, and
fDepartment of Veterinary Pathology, Freie Universit?t Berlin, Berlin, Germany;
gDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden;
hDepartment of Host Defence, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Address of Corresponding Author
J Innate Immun (DOI: 10.1159/000345112)
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Toll-like receptor 7
Innate immunity
Influenza A virus
Streptococcus pneumoniae
Bacterial superinfection
goto top of page 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.
Copyright ? 2012 S. Karger AG, Basel
http://content.karger.com/produktedb/produkte.asp?doi=345112
Sabine Stegemann-Koniszewskia, d, Marcus Gerekea, e, Sofia Orrskogg, Stefan Lienenklausb, Bastian Paschec, Sophie R. Baderf, Achim D. Gruberf, Shizuo Akirah, Siegfried Weissb, Birgitta Henriques-Normarkg, Dunja Brudera, e, Matthias Gunzerd
aImmune Regulation Group,
bMolecular Immunology and
cInfection Genetics, Helmholtz Centre for Infection Research, Braunschweig,
dInstitute of Experimental Immunology and Imaging, University Clinic, University of Duisburg-Essen, Essen,
eInfection Immunology Group, Department of Medical Microbiology, Otto von Guericke University Magdeburg, Magdeburg, and
fDepartment of Veterinary Pathology, Freie Universit?t Berlin, Berlin, Germany;
gDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden;
hDepartment of Host Defence, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Address of Corresponding Author
J Innate Immun (DOI: 10.1159/000345112)
goto top of page Key Words
Toll-like receptor 7
Innate immunity
Influenza A virus
Streptococcus pneumoniae
Bacterial superinfection
goto top of page 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.
Copyright ? 2012 S. Karger AG, Basel
http://content.karger.com/produktedb/produkte.asp?doi=345112