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Expression of TMPRSS2 is up-regulated by bacterial flagellin, LPS, and Pam3Cys in human airway cells.
Schwerdtner, Marie; Skalik, Annika; Limburg, Hannah; Bierwagen, Jeff; Jung, Anna Lena; Dorna, Jens; Kaufmann, Andreas; Bauer, Stefan; Schmeck, Bernd; Böttcher-Friebertshäuser, Eva.
  • Schwerdtner M; https://ror.org/01rdrb571 Institute of Virology, Philipps-University Marburg, Marburg, Germany.
  • Skalik A; https://ror.org/01rdrb571 Institute of Virology, Philipps-University Marburg, Marburg, Germany.
  • Limburg H; https://ror.org/01rdrb571 Institute of Virology, Philipps-University Marburg, Marburg, Germany.
  • Bierwagen J; https://ror.org/01rdrb571 Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany.
  • Jung AL; https://ror.org/01rdrb571 Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany.
  • Dorna J; https://ror.org/01rdrb571 Institute of Immunology, Philipps-University Marburg, Marburg, Germany.
  • Kaufmann A; https://ror.org/01rdrb571 Institute of Immunology, Philipps-University Marburg, Marburg, Germany.
  • Bauer S; https://ror.org/01rdrb571 Institute of Immunology, Philipps-University Marburg, Marburg, Germany.
  • Schmeck B; https://ror.org/01rdrb571 Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-University Marburg, German Center for Lung Research (DZL), Marburg, Germany.
  • Böttcher-Friebertshäuser E; https://ror.org/01rdrb571 Department of Pulmonary and Critical Care Medicine, Philipps-University Marburg, Marburg, Germany, Member of the German Center for Infectious Disease Research (DZIF), Marburg, Germany.
Life Sci Alliance ; 6(8)2023 08.
Article in English | MEDLINE | ID: covidwho-2326136
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 that Legionella pneumophila stimulates 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, and Streptococcus 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases Type of study: Prognostic study Limits: Humans Language: English Year: 2023 Document Type: Article Affiliation country: Lsa.202201813

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Serine Endopeptidases Type of study: Prognostic study Limits: Humans Language: English Year: 2023 Document Type: Article Affiliation country: Lsa.202201813