Allergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection

ABSTRACT Fatal outcomes following influenza infection are often associated with secondary bacterial infections. Allergic airway disease (AAD) is known to influence severe complications from respiratory infections, and yet the mechanistic effect of AAD on influenza virus-Streptococcus pneumoniae coin...

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Autores principales:	Sean Roberts, Sharon L. Salmon, Donald J. Steiner, Clare M. Williams, Dennis W. Metzger, Yoichi Furuya
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Streptococcus pneumoniae coinfection influenza interferon gamma Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9dd5786ecf724d57874c90af930d89a7
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spelling	oai:doaj.org-article:9dd5786ecf724d57874c90af930d89a72021-11-15T16:22:09ZAllergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection10.1128/mBio.01335-192150-7511https://doaj.org/article/9dd5786ecf724d57874c90af930d89a72019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01335-19https://doaj.org/toc/2150-7511ABSTRACT Fatal outcomes following influenza infection are often associated with secondary bacterial infections. Allergic airway disease (AAD) is known to influence severe complications from respiratory infections, and yet the mechanistic effect of AAD on influenza virus-Streptococcus pneumoniae coinfection has not been investigated previously. We examined the impact of AAD on host susceptibility to viral-bacterial coinfections. We report that AAD improved survival during coinfection when viral-bacterial challenge occurred 1 week after AAD. Counterintuitively, mice with AAD had significantly deceased proinflammatory responses during infection. Specifically, both CD4+ and CD8+ T cell interferon gamma (IFN-γ) responses were suppressed following AAD. Resistance to coinfection was also associated with strong transforming growth factor β1 (TGF-β1) expression and increased bacterial clearance. Treatment of AAD mice with IFN-γ or genetic deletion of TGF-β receptor II expression reversed the protective effects of AAD. Using a novel triple-challenge model system, we show for the first time that AAD can provide protection against influenza virus-S. pneumoniae coinfection through the production of TGF-β that suppresses the influenza virus-induced IFN-γ response, thereby preserving antibacterial immunity. IMPORTANCE Asthma has become one of the most common chronic diseases and has been identified as a risk factor for developing influenza. However, the impact of asthma on postinfluenza secondary bacterial infection is currently not known. Here, we developed a novel triple-challenge model of allergic airway disease, primary influenza infection, and secondary Streptococcus pneumoniae infection to investigate the impact of asthma on susceptibility to viral-bacterial coinfections. We report for the first time that mice recovering from acute allergic airway disease are highly resistant to influenza-pneumococcal coinfection and that this resistance is due to inhibition of influenza virus-mediated impairment of bacterial clearance. Further characterization of allergic airway disease-associated resistance against postinfluenza secondary bacterial infection may aid in the development of prophylactic and/or therapeutic treatment against coinfection.Sean RobertsSharon L. SalmonDonald J. SteinerClare M. WilliamsDennis W. MetzgerYoichi FuruyaAmerican Society for MicrobiologyarticleStreptococcus pneumoniaecoinfectioninfluenzainterferon gammaMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pneumoniae coinfection influenza interferon gamma Microbiology QR1-502
spellingShingle	Streptococcus pneumoniae coinfection influenza interferon gamma Microbiology QR1-502 Sean Roberts Sharon L. Salmon Donald J. Steiner Clare M. Williams Dennis W. Metzger Yoichi Furuya Allergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection
description	ABSTRACT Fatal outcomes following influenza infection are often associated with secondary bacterial infections. Allergic airway disease (AAD) is known to influence severe complications from respiratory infections, and yet the mechanistic effect of AAD on influenza virus-Streptococcus pneumoniae coinfection has not been investigated previously. We examined the impact of AAD on host susceptibility to viral-bacterial coinfections. We report that AAD improved survival during coinfection when viral-bacterial challenge occurred 1 week after AAD. Counterintuitively, mice with AAD had significantly deceased proinflammatory responses during infection. Specifically, both CD4+ and CD8+ T cell interferon gamma (IFN-γ) responses were suppressed following AAD. Resistance to coinfection was also associated with strong transforming growth factor β1 (TGF-β1) expression and increased bacterial clearance. Treatment of AAD mice with IFN-γ or genetic deletion of TGF-β receptor II expression reversed the protective effects of AAD. Using a novel triple-challenge model system, we show for the first time that AAD can provide protection against influenza virus-S. pneumoniae coinfection through the production of TGF-β that suppresses the influenza virus-induced IFN-γ response, thereby preserving antibacterial immunity. IMPORTANCE Asthma has become one of the most common chronic diseases and has been identified as a risk factor for developing influenza. However, the impact of asthma on postinfluenza secondary bacterial infection is currently not known. Here, we developed a novel triple-challenge model of allergic airway disease, primary influenza infection, and secondary Streptococcus pneumoniae infection to investigate the impact of asthma on susceptibility to viral-bacterial coinfections. We report for the first time that mice recovering from acute allergic airway disease are highly resistant to influenza-pneumococcal coinfection and that this resistance is due to inhibition of influenza virus-mediated impairment of bacterial clearance. Further characterization of allergic airway disease-associated resistance against postinfluenza secondary bacterial infection may aid in the development of prophylactic and/or therapeutic treatment against coinfection.
format	article
author	Sean Roberts Sharon L. Salmon Donald J. Steiner Clare M. Williams Dennis W. Metzger Yoichi Furuya
author_facet	Sean Roberts Sharon L. Salmon Donald J. Steiner Clare M. Williams Dennis W. Metzger Yoichi Furuya
author_sort	Sean Roberts
title	Allergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection
title_short	Allergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection
title_full	Allergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection
title_fullStr	Allergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection
title_full_unstemmed	Allergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection
title_sort	allergic airway disease prevents lethal synergy of influenza a virus-<named-content content-type="genus-species">streptococcus pneumoniae</named-content> coinfection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/9dd5786ecf724d57874c90af930d89a7
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Allergic Airway Disease Prevents Lethal Synergy of Influenza A Virus-<named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection

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