Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine Lung
Influenza A virus pathogenesis may differ between men and women. The 2009 H1N1 influenza pandemic resulted in more documented hospitalizations in women compared to men. In this study, we analyzed the impact of male sex hormones on pandemic 2009 H1N1 influenza A virus disease outcome. In a murine inf...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00697/full |
| _version_ | 1811288346807238656 |
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| author | Berfin Tuku Stephanie Stanelle-Bertram Julie Sellau Sebastian Beck Tian Bai Nancy Mounogou Kouassi Annette Preuß Stefan Hoenow Thomas Renné Hanna Lotter Gülsah Gabriel Gülsah Gabriel |
| author_facet | Berfin Tuku Stephanie Stanelle-Bertram Julie Sellau Sebastian Beck Tian Bai Nancy Mounogou Kouassi Annette Preuß Stefan Hoenow Thomas Renné Hanna Lotter Gülsah Gabriel Gülsah Gabriel |
| author_sort | Berfin Tuku |
| collection | DOAJ |
| description | Influenza A virus pathogenesis may differ between men and women. The 2009 H1N1 influenza pandemic resulted in more documented hospitalizations in women compared to men. In this study, we analyzed the impact of male sex hormones on pandemic 2009 H1N1 influenza A virus disease outcome. In a murine infection model, we could mimic the clinical findings with female mice undergoing severe and even fatal 2009 H1N1 influenza compared to male mice. Treatment of female mice with testosterone could rescue the majority of mice from lethal influenza. Improved disease outcome in testosterone treated female mice upon 2009 H1N1 influenza A virus infection did not affect virus titers in the lung compared to carrier-treated females. However, reduction in IL-1β cytokine expression levels strongly correlated with reduced lung damage and improved influenza disease outcome in female mice upon testosterone treatment. In contrast, influenza disease outcome was not affected between castrated male mice and non-castrated controls. Here, influenza infection resulted in reduction of testosterone expression in male mice. These findings show that testosterone has protective functions on the influenza infection course. However, 2009 H1N1 influenza viruses seem to have evolved yet unknown mechanisms to reduce testosterone expression in males. These data will support future antiviral strategies to treat influenza taking sex-dependent immunopathologies into consideration. |
| first_indexed | 2024-04-13T03:35:34Z |
| format | Article |
| id | doaj.art-0ba9b0f1ab874631ae1687d1d60c73da |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T03:35:34Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0ba9b0f1ab874631ae1687d1d60c73da2022-12-22T03:04:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-04-011110.3389/fimmu.2020.00697521319Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine LungBerfin Tuku0Stephanie Stanelle-Bertram1Julie Sellau2Sebastian Beck3Tian Bai4Nancy Mounogou Kouassi5Annette Preuß6Stefan Hoenow7Thomas Renné8Hanna Lotter9Gülsah Gabriel10Gülsah Gabriel11Department Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, GermanyDepartment Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, GermanyResearch Group Molecular Infection Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyDepartment Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, GermanyDepartment Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, GermanyDepartment Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, GermanyDepartment Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, GermanyResearch Group Molecular Infection Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyInstitute for Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyResearch Group Molecular Infection Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, GermanyDepartment Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, GermanyInstitute of Virology, University of Veterinary Medicine Hannover, Hanover, GermanyInfluenza A virus pathogenesis may differ between men and women. The 2009 H1N1 influenza pandemic resulted in more documented hospitalizations in women compared to men. In this study, we analyzed the impact of male sex hormones on pandemic 2009 H1N1 influenza A virus disease outcome. In a murine infection model, we could mimic the clinical findings with female mice undergoing severe and even fatal 2009 H1N1 influenza compared to male mice. Treatment of female mice with testosterone could rescue the majority of mice from lethal influenza. Improved disease outcome in testosterone treated female mice upon 2009 H1N1 influenza A virus infection did not affect virus titers in the lung compared to carrier-treated females. However, reduction in IL-1β cytokine expression levels strongly correlated with reduced lung damage and improved influenza disease outcome in female mice upon testosterone treatment. In contrast, influenza disease outcome was not affected between castrated male mice and non-castrated controls. Here, influenza infection resulted in reduction of testosterone expression in male mice. These findings show that testosterone has protective functions on the influenza infection course. However, 2009 H1N1 influenza viruses seem to have evolved yet unknown mechanisms to reduce testosterone expression in males. These data will support future antiviral strategies to treat influenza taking sex-dependent immunopathologies into consideration.https://www.frontiersin.org/article/10.3389/fimmu.2020.00697/fullinfluenza A virussex differencestestosterone2009 H1N1androgens |
| spellingShingle | Berfin Tuku Stephanie Stanelle-Bertram Julie Sellau Sebastian Beck Tian Bai Nancy Mounogou Kouassi Annette Preuß Stefan Hoenow Thomas Renné Hanna Lotter Gülsah Gabriel Gülsah Gabriel Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine Lung Frontiers in Immunology influenza A virus sex differences testosterone 2009 H1N1 androgens |
| title | Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine Lung |
| title_full | Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine Lung |
| title_fullStr | Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine Lung |
| title_full_unstemmed | Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine Lung |
| title_short | Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine Lung |
| title_sort | testosterone protects against severe influenza by reducing the pro inflammatory cytokine response in the murine lung |
| topic | influenza A virus sex differences testosterone 2009 H1N1 androgens |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00697/full |
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