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NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice

The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inf...

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Autores principales: Hofstetter, Amelia R., De La Cruz, Juan A., Cao, Weiping, Patel, Jenish, Belser, Jessica A., McCoy, James, Liepkalns, Justine S., Amoah, Samuel, Cheng, Guangjie, Ranjan, Priya, Diebold, Becky A., Shieh, Wun-Ju, Zaki, Sherif, Katz, Jacqueline M., Sambhara, Suryaprakash, Lambeth, J. David, Gangappa, Shivaprakash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766197/
https://www.ncbi.nlm.nih.gov/pubmed/26910342
http://dx.doi.org/10.1371/journal.pone.0149864
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author Hofstetter, Amelia R.
De La Cruz, Juan A.
Cao, Weiping
Patel, Jenish
Belser, Jessica A.
McCoy, James
Liepkalns, Justine S.
Amoah, Samuel
Cheng, Guangjie
Ranjan, Priya
Diebold, Becky A.
Shieh, Wun-Ju
Zaki, Sherif
Katz, Jacqueline M.
Sambhara, Suryaprakash
Lambeth, J. David
Gangappa, Shivaprakash
author_facet Hofstetter, Amelia R.
De La Cruz, Juan A.
Cao, Weiping
Patel, Jenish
Belser, Jessica A.
McCoy, James
Liepkalns, Justine S.
Amoah, Samuel
Cheng, Guangjie
Ranjan, Priya
Diebold, Becky A.
Shieh, Wun-Ju
Zaki, Sherif
Katz, Jacqueline M.
Sambhara, Suryaprakash
Lambeth, J. David
Gangappa, Shivaprakash
author_sort Hofstetter, Amelia R.
collection PubMed
description The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inflammation in mice within 7 days post-influenza A virus infection. However, the effect of NADPH oxidase 1 on lethality and adaptive immunity after influenza A virus challenge has not been explored. Here we report improved survival and decreased morbidity in mice with catalytically inactive NADPH oxidase 1 (Nox1*(/Y)) compared with controls after challenge with A/PR/8/34 influenza A virus. While changes in lung inflammation were not obvious between Nox1*(/Y) and control mice, we observed alterations in the T cell response to influenza A virus by day 15 post-infection, including increased interleukin-7 receptor-expressing virus-specific CD8(+) T cells in lungs and draining lymph nodes of Nox1*(/Y), and increased cytokine-producing T cells in lungs and spleen. Furthermore, a greater percentage of conventional and interstitial dendritic cells from Nox1*(/Y) draining lymph nodes expressed the co-stimulatory ligand CD40 within 6 days post-infection. Results indicate that NADPH oxidase 1 modulates the innate and adaptive cellular immune response to influenza virus infection, while also playing a role in host survival. Results suggest that NADPH oxidase 1 inhibitors may be beneficial as adjunct therapeutics during acute influenza infection.
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spelling pubmed-47661972016-02-26 NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice Hofstetter, Amelia R. De La Cruz, Juan A. Cao, Weiping Patel, Jenish Belser, Jessica A. McCoy, James Liepkalns, Justine S. Amoah, Samuel Cheng, Guangjie Ranjan, Priya Diebold, Becky A. Shieh, Wun-Ju Zaki, Sherif Katz, Jacqueline M. Sambhara, Suryaprakash Lambeth, J. David Gangappa, Shivaprakash PLoS One Research Article The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inflammation in mice within 7 days post-influenza A virus infection. However, the effect of NADPH oxidase 1 on lethality and adaptive immunity after influenza A virus challenge has not been explored. Here we report improved survival and decreased morbidity in mice with catalytically inactive NADPH oxidase 1 (Nox1*(/Y)) compared with controls after challenge with A/PR/8/34 influenza A virus. While changes in lung inflammation were not obvious between Nox1*(/Y) and control mice, we observed alterations in the T cell response to influenza A virus by day 15 post-infection, including increased interleukin-7 receptor-expressing virus-specific CD8(+) T cells in lungs and draining lymph nodes of Nox1*(/Y), and increased cytokine-producing T cells in lungs and spleen. Furthermore, a greater percentage of conventional and interstitial dendritic cells from Nox1*(/Y) draining lymph nodes expressed the co-stimulatory ligand CD40 within 6 days post-infection. Results indicate that NADPH oxidase 1 modulates the innate and adaptive cellular immune response to influenza virus infection, while also playing a role in host survival. Results suggest that NADPH oxidase 1 inhibitors may be beneficial as adjunct therapeutics during acute influenza infection. Public Library of Science 2016-02-24 /pmc/articles/PMC4766197/ /pubmed/26910342 http://dx.doi.org/10.1371/journal.pone.0149864 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Hofstetter, Amelia R.
De La Cruz, Juan A.
Cao, Weiping
Patel, Jenish
Belser, Jessica A.
McCoy, James
Liepkalns, Justine S.
Amoah, Samuel
Cheng, Guangjie
Ranjan, Priya
Diebold, Becky A.
Shieh, Wun-Ju
Zaki, Sherif
Katz, Jacqueline M.
Sambhara, Suryaprakash
Lambeth, J. David
Gangappa, Shivaprakash
NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice
title NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice
title_full NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice
title_fullStr NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice
title_full_unstemmed NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice
title_short NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice
title_sort nadph oxidase 1 is associated with altered host survival and t cell phenotypes after influenza a virus infection in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766197/
https://www.ncbi.nlm.nih.gov/pubmed/26910342
http://dx.doi.org/10.1371/journal.pone.0149864
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