Expression of TMPRSS2 is up-regulated by bacterial flagellin, LPS, and Pam3Cys in human airway cells

Author:

Schwerdtner Marie1,Skalik Annika1,Limburg Hannah1,Bierwagen Jeff2ORCID,Jung Anna Lena2,Dorna Jens3,Kaufmann Andreas3,Bauer Stefan3ORCID,Schmeck Bernd24,Böttcher-Friebertshäuser Eva1ORCID

Affiliation:

1. Institute of Virology, Philipps-University Marburg

2. Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg

3. Institute of Immunology, Philipps-University Marburg

4. Department of Pulmonary and Critical Care Medicine, Philipps-University Marburg

Abstract

Many viruses require proteolytic activation of their envelope proteins for infectivity, and relevant host proteases provide promising drug targets. The transmembrane serine protease 2 (TMPRSS2) has been identified as a major activating protease of influenza A virus (IAV) and various coronaviruses (CoV). Increased TMPRSS2 expression has been associated with a higher risk of severe influenza infection and enhanced susceptibility to SARS-CoV-2. Here, we found thatLegionella pneumophilastimulates the increased expression of TMPRSS2-mRNA in Calu-3 human airway cells. We identified flagellin as the dominant structural component inducing TMPRSS2 expression. The flagellin-induced increase was not observed at this magnitude for other virus-activating host proteases. TMPRSS2-mRNA expression was also significantly increased by LPS, Pam3Cys, andStreptococcus pneumoniae, although less pronounced. Multicycle replication of H1N1pdm and H3N2 IAV but not SARS-CoV-2 and SARS-CoV was enhanced by flagellin treatment. Our data suggest that bacteria, particularly flagellated bacteria, up-regulate the expression of TMPRSS2 in human airway cells and, thereby, may support enhanced activation and replication of IAV upon co-infections. In addition, our data indicate a physiological role of TMPRSS2 in antimicrobial host response.

Funder

Deutsche Forschungsgemeinschaft

Universities of Giessen and Marburg

Hessisches Ministerium für Wissenschaft und Kunst

Publisher

Life Science Alliance, LLC

Subject

Health, Toxicology and Mutagenesis,Plant Science,Biochemistry, Genetics and Molecular Biology (miscellaneous),Ecology

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