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Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and Streptococcus pneumoniae Coinfection Is Associated with Loss of Murine Lung Repair Responses

Secondary bacterial infections increase disease severity of influenza virus infections and contribute greatly to increased morbidity and mortality during pandemics. To study secondary bacterial infection following influenza virus infection, mice were inoculated with sublethal doses of 2009 seasonal...

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Autores principales: Kash, John C., Walters, Kathie-Anne, Davis, A. Sally, Sandouk, Aline, Schwartzman, Louis M., Jagger, Brett W., Chertow, Daniel S., Li, Qi, Kuestner, Rolf E., Ozinsky, Adrian, Taubenberger, Jeffery K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175626/
https://www.ncbi.nlm.nih.gov/pubmed/21933918
http://dx.doi.org/10.1128/mBio.00172-11
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author Kash, John C.
Walters, Kathie-Anne
Davis, A. Sally
Sandouk, Aline
Schwartzman, Louis M.
Jagger, Brett W.
Chertow, Daniel S.
Li, Qi
Kuestner, Rolf E.
Ozinsky, Adrian
Taubenberger, Jeffery K.
author_facet Kash, John C.
Walters, Kathie-Anne
Davis, A. Sally
Sandouk, Aline
Schwartzman, Louis M.
Jagger, Brett W.
Chertow, Daniel S.
Li, Qi
Kuestner, Rolf E.
Ozinsky, Adrian
Taubenberger, Jeffery K.
author_sort Kash, John C.
collection PubMed
description Secondary bacterial infections increase disease severity of influenza virus infections and contribute greatly to increased morbidity and mortality during pandemics. To study secondary bacterial infection following influenza virus infection, mice were inoculated with sublethal doses of 2009 seasonal H1N1 virus (NIH50) or pandemic H1N1 virus (Mex09) followed by inoculation with Streptococcus pneumoniae 48 h later. Disease was characterized by assessment of weight loss and survival, titration of virus and bacteria by quantitative reverse transcription-PCR (qRT-PCR), histopathology, expression microarray, and immunohistochemistry. Mice inoculated with virus alone showed 100% survival for all groups. Mice inoculated with Mex09 plus S. pneumoniae showed severe weight loss and 100% mortality with severe alveolitis, denuded bronchiolar epithelium, and widespread expression of apoptosis marker cleaved caspase 3. In contrast, mice inoculated with NIH50 plus S. pneumoniae showed increased weight loss, 100% survival, and slightly enhanced lung pathology. Mex09-S. pneumoniae coinfection also resulted in increased S. pneumoniae replication in lung and bacteremia late in infection. Global gene expression profiling revealed that Mex09-S. pneumoniae coinfection did not induce significantly more severe inflammatory responses but featured significant loss of epithelial cell reproliferation and repair responses. Histopathological examination for cell proliferation marker MCM7 showed significant staining of airway epithelial cells in all groups except Mex09-S. pneumoniae-infected mice. This study demonstrates that secondary bacterial infection during 2009 H1N1 pandemic virus infection resulted in more severe disease and loss of lung repair responses than did seasonal influenza viral and bacterial coinfection. Moreover, this study provides novel insights into influenza virus and bacterial coinfection by showing correlation of lethal outcome with loss of airway basal epithelial cells and associated lung repair responses.
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spelling pubmed-31756262011-09-20 Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and Streptococcus pneumoniae Coinfection Is Associated with Loss of Murine Lung Repair Responses Kash, John C. Walters, Kathie-Anne Davis, A. Sally Sandouk, Aline Schwartzman, Louis M. Jagger, Brett W. Chertow, Daniel S. Li, Qi Kuestner, Rolf E. Ozinsky, Adrian Taubenberger, Jeffery K. mBio Research Article Secondary bacterial infections increase disease severity of influenza virus infections and contribute greatly to increased morbidity and mortality during pandemics. To study secondary bacterial infection following influenza virus infection, mice were inoculated with sublethal doses of 2009 seasonal H1N1 virus (NIH50) or pandemic H1N1 virus (Mex09) followed by inoculation with Streptococcus pneumoniae 48 h later. Disease was characterized by assessment of weight loss and survival, titration of virus and bacteria by quantitative reverse transcription-PCR (qRT-PCR), histopathology, expression microarray, and immunohistochemistry. Mice inoculated with virus alone showed 100% survival for all groups. Mice inoculated with Mex09 plus S. pneumoniae showed severe weight loss and 100% mortality with severe alveolitis, denuded bronchiolar epithelium, and widespread expression of apoptosis marker cleaved caspase 3. In contrast, mice inoculated with NIH50 plus S. pneumoniae showed increased weight loss, 100% survival, and slightly enhanced lung pathology. Mex09-S. pneumoniae coinfection also resulted in increased S. pneumoniae replication in lung and bacteremia late in infection. Global gene expression profiling revealed that Mex09-S. pneumoniae coinfection did not induce significantly more severe inflammatory responses but featured significant loss of epithelial cell reproliferation and repair responses. Histopathological examination for cell proliferation marker MCM7 showed significant staining of airway epithelial cells in all groups except Mex09-S. pneumoniae-infected mice. This study demonstrates that secondary bacterial infection during 2009 H1N1 pandemic virus infection resulted in more severe disease and loss of lung repair responses than did seasonal influenza viral and bacterial coinfection. Moreover, this study provides novel insights into influenza virus and bacterial coinfection by showing correlation of lethal outcome with loss of airway basal epithelial cells and associated lung repair responses. American Society of Microbiology 2011-09-20 /pmc/articles/PMC3175626/ /pubmed/21933918 http://dx.doi.org/10.1128/mBio.00172-11 Text en Copyright © 2011 Kash et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kash, John C.
Walters, Kathie-Anne
Davis, A. Sally
Sandouk, Aline
Schwartzman, Louis M.
Jagger, Brett W.
Chertow, Daniel S.
Li, Qi
Kuestner, Rolf E.
Ozinsky, Adrian
Taubenberger, Jeffery K.
Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and Streptococcus pneumoniae Coinfection Is Associated with Loss of Murine Lung Repair Responses
title Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and Streptococcus pneumoniae Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_full Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and Streptococcus pneumoniae Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_fullStr Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and Streptococcus pneumoniae Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_full_unstemmed Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and Streptococcus pneumoniae Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_short Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and Streptococcus pneumoniae Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_sort lethal synergism of 2009 pandemic h1n1 influenza virus and streptococcus pneumoniae coinfection is associated with loss of murine lung repair responses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175626/
https://www.ncbi.nlm.nih.gov/pubmed/21933918
http://dx.doi.org/10.1128/mBio.00172-11
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