Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine Lung
Identifieur interne : 002124 ( Ncbi/Checkpoint ); précédent : 002123; suivant : 002125Testosterone Protects Against Severe Influenza by Reducing the Pro-Inflammatory Cytokine Response in the Murine Lung
Auteurs : Berfin Tuku [Allemagne] ; Stephanie Stanelle-Bertram [Allemagne] ; Julie Sellau [Allemagne] ; Sebastian Beck [Allemagne] ; Tian Bai [Allemagne] ; Nancy Mounogou Kouassi [Allemagne] ; Annette Preu [Allemagne] ; Stefan Hoenow [Allemagne] ; Thomas Renné [Allemagne] ; Hanna Lotter [Allemagne] ; Gülsah Gabriel [Allemagne]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2020.
Abstract
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.
Url:
DOI: 10.3389/fimmu.2020.00697
PubMed: 32431696
PubMed Central: 7216738
Affiliations:
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One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Stanelle Bertram, Stephanie" sort="Stanelle Bertram, Stephanie" uniqKey="Stanelle Bertram S" first="Stephanie" last="Stanelle-Bertram">Stephanie Stanelle-Bertram</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sellau, Julie" sort="Sellau, Julie" uniqKey="Sellau J" first="Julie" last="Sellau">Julie Sellau</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Research Group Molecular Infection Immunology, Bernhard Nocht Institute for Tropical Medicine</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Beck, Sebastian" sort="Beck, Sebastian" uniqKey="Beck S" first="Sebastian" last="Beck">Sebastian Beck</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bai, Tian" sort="Bai, Tian" uniqKey="Bai T" first="Tian" last="Bai">Tian Bai</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kouassi, Nancy Mounogou" sort="Kouassi, Nancy Mounogou" uniqKey="Kouassi N" first="Nancy Mounogou" last="Kouassi">Nancy Mounogou Kouassi</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Preu, Annette" sort="Preu, Annette" uniqKey="Preu A" first="Annette" last="Preu">Annette Preu</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hoenow, Stefan" sort="Hoenow, Stefan" uniqKey="Hoenow S" first="Stefan" last="Hoenow">Stefan Hoenow</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Research Group Molecular Infection Immunology, Bernhard Nocht Institute for Tropical Medicine</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Renne, Thomas" sort="Renne, Thomas" uniqKey="Renne T" first="Thomas" last="Renné">Thomas Renné</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lotter, Hanna" sort="Lotter, Hanna" uniqKey="Lotter H" first="Hanna" last="Lotter">Hanna Lotter</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Research Group Molecular Infection Immunology, Bernhard Nocht Institute for Tropical Medicine</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gabriel, Gulsah" sort="Gabriel, Gulsah" uniqKey="Gabriel G" first="Gülsah" last="Gabriel">Gülsah Gabriel</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department Viral Zoonoses - One Health, Heinrich Pette Institute, Leibniz Institute for Experimental Virology</institution>,<addr-line>Hamburg</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Institute of Virology, University of Veterinary Medicine Hannover</institution>,<addr-line>Hanover</addr-line>,<country>Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Immunology</title><idno type="eISSN">1664-3224</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Klein, Sl" uniqKey="Klein S">SL Klein</name></author><author><name sortKey="Hodgson, A" uniqKey="Hodgson A">A Hodgson</name></author><author><name sortKey="Robinson, Dp" uniqKey="Robinson D">DP. 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Klein</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Allemagne</li></country></list><tree><country name="Allemagne"><noRegion><name sortKey="Tuku, Berfin" sort="Tuku, Berfin" uniqKey="Tuku B" first="Berfin" last="Tuku">Berfin Tuku</name></noRegion><name sortKey="Bai, Tian" sort="Bai, Tian" uniqKey="Bai T" first="Tian" last="Bai">Tian Bai</name><name sortKey="Beck, Sebastian" sort="Beck, Sebastian" uniqKey="Beck S" first="Sebastian" last="Beck">Sebastian Beck</name><name sortKey="Gabriel, Gulsah" sort="Gabriel, Gulsah" uniqKey="Gabriel G" first="Gülsah" last="Gabriel">Gülsah Gabriel</name><name sortKey="Gabriel, Gulsah" sort="Gabriel, Gulsah" uniqKey="Gabriel G" first="Gülsah" last="Gabriel">Gülsah Gabriel</name><name sortKey="Hoenow, Stefan" sort="Hoenow, Stefan" uniqKey="Hoenow S" first="Stefan" last="Hoenow">Stefan Hoenow</name><name sortKey="Kouassi, Nancy Mounogou" sort="Kouassi, Nancy Mounogou" uniqKey="Kouassi N" first="Nancy Mounogou" last="Kouassi">Nancy Mounogou Kouassi</name><name sortKey="Lotter, Hanna" sort="Lotter, Hanna" uniqKey="Lotter H" first="Hanna" last="Lotter">Hanna Lotter</name><name sortKey="Preu, Annette" sort="Preu, Annette" uniqKey="Preu A" first="Annette" last="Preu">Annette Preu</name><name sortKey="Renne, Thomas" sort="Renne, Thomas" uniqKey="Renne T" first="Thomas" last="Renné">Thomas Renné</name><name sortKey="Sellau, Julie" sort="Sellau, Julie" uniqKey="Sellau J" first="Julie" last="Sellau">Julie Sellau</name><name sortKey="Stanelle Bertram, Stephanie" sort="Stanelle Bertram, Stephanie" uniqKey="Stanelle Bertram S" first="Stephanie" last="Stanelle-Bertram">Stephanie Stanelle-Bertram</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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