Journalartikel

Streptococcus pneumoniae Stimulates a STING- and IFN Regulatory Factor 3-Dependent Type I IFN Production in Macrophages, which Regulates RANTES Production in Macrophages, Cocultured Alveolar Epithelial Cells, and Mouse Lungs


AutorenlisteKoppe, Uwe; Hoegner, Katrin; Doehn, Jan-Moritz; Mueller, Holger C.; Witzenrath, Martin; Gutbier, Birgitt; Bauer, Stefan; Pribyl, Thomas; Hammerschmidt, Sven; Lohmeyer, Juergen; Suttorp, Norbert; Herold, Susanne; Opitz, Bastian

Jahr der Veröffentlichung2012

Seiten811-817

ZeitschriftThe Journal of Immunology

Bandnummer188

Heftnummer2

ISSN0022-1767

DOI Linkhttps://doi.org/10.4049/jimmunol.1004143

VerlagAmerican Association of Immunologists


Abstract
Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. In this study, we examine an innate immune recognition pathway that senses pneumococcal infection, triggers type I IFN production, and regulates RANTES production. We found that human and murine alveolar macrophages as well as murine bone marrow macrophages, but not alveolar epithelial cells, produced type I IFNs upon infection with S. pneumoniae. This response was dependent on the pore-forming toxin pneumolysin and appeared to be mediated by a cytosolic DNA-sensing pathway involving the adapter molecule STING and the transcription factor IFN regulatory factor 3. Indeed, DNA was present in the cytosol during pneumococcal infection as indicated by the activation of the AIM2 inflammasome, which is known to sense microbial DNA. Type I IFNs produced by S. pneumoniae-infected macrophages positively regulated gene expression and RANTES production in macrophages and cocultured alveolar epithelial cells in vitro. Moreover, type I IFNs controlled RANTES production during pneumococcal pneumonia in vivo. In conclusion, we identified an immune sensing pathway detecting S. pneumoniae that triggers a type I IFN response and positively regulates RANTES production. The Journal of Immunology, 2012, 188: 811-817.



Zitierstile

Harvard-ZitierstilKoppe, U., Hoegner, K., Doehn, J., Mueller, H., Witzenrath, M., Gutbier, B., et al. (2012) Streptococcus pneumoniae Stimulates a STING- and IFN Regulatory Factor 3-Dependent Type I IFN Production in Macrophages, which Regulates RANTES Production in Macrophages, Cocultured Alveolar Epithelial Cells, and Mouse Lungs, The Journal of Immunology, 188(2), pp. 811-817. https://doi.org/10.4049/jimmunol.1004143

APA-ZitierstilKoppe, U., Hoegner, K., Doehn, J., Mueller, H., Witzenrath, M., Gutbier, B., Bauer, S., Pribyl, T., Hammerschmidt, S., Lohmeyer, J., Suttorp, N., Herold, S., & Opitz, B. (2012). Streptococcus pneumoniae Stimulates a STING- and IFN Regulatory Factor 3-Dependent Type I IFN Production in Macrophages, which Regulates RANTES Production in Macrophages, Cocultured Alveolar Epithelial Cells, and Mouse Lungs. The Journal of Immunology. 188(2), 811-817. https://doi.org/10.4049/jimmunol.1004143



Schlagwörter


AIM2 INFLAMMASOMECYTOSOLIC DNAHOST-DEFENSEinterferon responseINTRACELLULAR DNALISTERIA-MONOCYTOGENESPNEUMOCOCCAL PNEUMONIA


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