title: Mitogen-activated protein kinases (MAPKs) regulate IL-6 over-production during concomitant influenza virus and Staphylococcus aureus infection.
abstract: Bacterial super-infections are a major complication of influenza virus (IV) infections and often lead to severe pneumonia. One hallmark of IV-associated Staphylococcus aureus (S. aureus) infection is rapid progression to a serious disease outcome. Changes in immune and inflammatory host responses increase morbidity and complicate efficient therapy. A key player during inflammation is the multifunctional cytokine IL-6. Although increased IL-6 levels have been observed after severe disease upon IV and/or bacterial super-infection, the underlying molecular mechanisms still remain to be elucidated. In the present study, we focused on cellular signalling pathways regulating IL-6 production upon IV/S. aureus super-infection. Additionally, infection with viable bacteria was mimicked by lipoteichoic acid stimulation in this model. Analyses of cellular signalling mechanisms revealed synergistically increased activation of the MAPK p38 as well as enhanced phosphorylation of the MAPKs ERK1/2 and JNK in the presence of super-infecting bacteria. Interestingly, inhibition of MAPK activity indicated a strong dependence of IL-6 expression on p38 and ERK1/2, while the MAPK JNK seems not to be involved. Thus, our results provide new molecular insights into the regulation of IL-6, a marker of severe disease, which might contribute to the lethal synergism of IV and S. aureus.
authors.affiliation: Institute of Virology Muenster (IVM), Westfaelische Wilhelms-University Muenster, Von Esmarch-Str. 56, D-48149 Muenster, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Klemm
authors.affiliation: Institute of Virology Muenster (IVM), Westfaelische Wilhelms-University Muenster, Von Esmarch-Str. 56, D-48149 Muenster, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Bruchhagen
authors.affiliation: Institute of Virology Muenster (IVM), Westfaelische Wilhelms-University Muenster, Von Esmarch-Str. 56, D-48149 Muenster, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: van Krüchten
authors.affiliation: Institute of Medical Microbiology, University Hospital of Muenster, Domagkstr, 10, D-48149 Muenster, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Niemann
authors.affiliation: Institute of Medical Microbiology, University Hospital Jena, Erlanger Allee 101, D-07747 Jena, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Löffler
authors.affiliation: Institute of Medical Microbiology, University Hospital of Muenster, Domagkstr, 10, D-48149 Muenster, Germany.|Cluster of Excellence Cells in Motion (CIM), University of Muenster, Muenster, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Peters
authors.affiliation: Institute of Virology Muenster (IVM), Westfaelische Wilhelms-University Muenster, Von Esmarch-Str. 56, D-48149 Muenster, Germany.|Cluster of Excellence Cells in Motion (CIM), University of Muenster, Muenster, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
authors.affiliation: Institute of Virology Muenster (IVM), Westfaelische Wilhelms-University Muenster, Von Esmarch-Str. 56, D-48149 Muenster, Germany.|Cluster of Excellence Cells in Motion (CIM), University of Muenster, Muenster, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
mesh_terms: D015415:Biomarkers; D002460:Cell Line; D060085:Coinfection; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007251:Influenza, Human / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D013203:Staphylococcal Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D012333:RNA, Messenger; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054648:Protein Phosphatase 2