title: MicroRNAs Constitute a Negative Feedback Loop in Streptococcus pneumoniae-Induced Macrophage Activation.
abstract: Streptococcus pneumoniae causes high mortality as a major pneumonia-inducing pathogen. In pneumonia, control of innate immunity is necessary to prevent organ damage. We assessed the role of microRNAs (miRNAs) as regulators in pneumococcal infection of human macrophages. Exposure of primary blood-derived human macrophages with pneumococci resulted in transcriptional changes in several gene clusters and a significant deregulation of 10 microRNAs. Computational network analysis retrieved miRNA-146a as one putatively important regulator of pneumococci-induced host cell activation. Its induction depended on bacterial structural integrity and was completely inhibited by blocking Toll-like receptor 2 (TLR-2) or depleting its mediator MyD88. Furthermore, induction of miRNA-146a release did not require the autocrine feedback of interleukin 1β and tumor necrosis factor α released from infected macrophages, and it repressed the TLR-2 downstream mediators IRAK-1 and TRAF-6, as well as the inflammatory factors cyclooxygenase 2 and interleukin 1β. In summary, pneumococci recognition induces a negative feedback loop, preventing excessive inflammation via miR-146a and potentially other miRNAs.
authors.affiliation: Institute for Lung Research, German Center for Lung Research, Universities of Giessen and Marburg Lung Center Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Griss
authors.affiliation: Institute for Lung Research, German Center for Lung Research, Universities of Giessen and Marburg Lung Center.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bertrams
authors.affiliation: Institute for Lung Research, German Center for Lung Research, Universities of Giessen and Marburg Lung Center.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sittka-Stark
authors.affiliation: Institute for Lung Research, German Center for Lung Research, Universities of Giessen and Marburg Lung Center.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Seidel
authors.affiliation: Institute for Lung Research, German Center for Lung Research, Universities of Giessen and Marburg Lung Center.
authors.forename: Christina
authors.initials: C
authors.lastname: Stielow
authors.affiliation: Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
authors.affiliation: Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin.
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.affiliation: Laboratory of Systems Tumor Immunology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nuremberg and University Hospital of Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eberhardt
authors.affiliation: Universities of Giessen and Marburg Lung Center, German Center for Lung Research (DZL), Justus-Liebig-University Giessen.
authors.forename: Jochen
authors.initials: J
authors.lastname: Wilhelm
authors.affiliation: Laboratory of Systems Tumor Immunology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nuremberg and University Hospital of Erlangen, Germany.
authors.forename: Julio
authors.initials: J
authors.lastname: Vera
authors.affiliation: Institute for Lung Research, German Center for Lung Research, Universities of Giessen and Marburg Lung Center Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schmeck
mesh_terms: D002478:Cells, Cultured; D025461:Feedback, Physiological; D020869:Gene Expression Profiling; D006801:Humans; D008262:Macrophage Activation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs
keywords: Streptococcus pneumoniae; macrophages; microRNA