Mitogen-activated protein kinases (MAPKs) regulate IL-6 over-production during concomitant influenza virus and Staphylococcus aureus infection

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 in...

Authors: Klemm, Carolin Ines
Bruchhagen, Christin
Krüchten, Andre
Niemann, Silke
Löffler, Bettina
Peters, Georg
Ludwig, Stephan
Ehrhardt, Christina
Division/Institute:FB 05: Medizinische Fakultät
FB 13: Biologie
Document types:Article
Media types:Text
Publication date:2017
Date of publication on miami:09.10.2018
Modification date:16.04.2019
Edition statement:[Electronic ed.]
Source:Scientific Reports 7 (2017) 42473, 1-15
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2017 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
URN:urn:nbn:de:hbz:6-87119724048
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-87119724048
Other Identifiers:DOI: 10.1038/srep42473
Digital documents:srep42473.pdf

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.