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Altered transcriptional responses in the lungs of aged mice after influenza infection

BACKGROUND: Influenza causes a serious infection in older individuals who are at the highest risk for mortality from this virus. Changes in the immune system with age are well known. This study used transcriptomic analysis to evaluate how aging specifically affects the functional host response to in...

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Autores principales: Hernandez, Ana M., Mossman, Jim A., Toapanta, Franklin R., Previte, Dana M., Ross, Ted M., Nau, Gerard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158162/
https://www.ncbi.nlm.nih.gov/pubmed/35650631
http://dx.doi.org/10.1186/s12979-022-00286-9
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author Hernandez, Ana M.
Mossman, Jim A.
Toapanta, Franklin R.
Previte, Dana M.
Ross, Ted M.
Nau, Gerard J.
author_facet Hernandez, Ana M.
Mossman, Jim A.
Toapanta, Franklin R.
Previte, Dana M.
Ross, Ted M.
Nau, Gerard J.
author_sort Hernandez, Ana M.
collection PubMed
description BACKGROUND: Influenza causes a serious infection in older individuals who are at the highest risk for mortality from this virus. Changes in the immune system with age are well known. This study used transcriptomic analysis to evaluate how aging specifically affects the functional host response to influenza in the lung. Adult (12–16 weeks) and aged (72–76 weeks) mice were infected with influenza and lungs were processed for RNA analysis. RESULTS: Older mice demonstrated a delayed anti-viral response on the level of transcription compared to adults, similar to the immunologic responses measured in prior work. The transcriptional differences, however, were evident days before observable differences in the protein responses described previously. The transcriptome response to influenza in aged mice was dominated by immunoglobulin genes and B cell markers compared to adult animals, suggesting immune dysregulation. Despite these differences, both groups of mice had highly similar transcriptional responses involving non-immune genes one day after inoculation and T cell genes during resolution. CONCLUSIONS: These results define a delayed and dysregulated immune response in the lungs of aged mice infected with influenza. The findings implicate B cells and immunoglobulins as markers or mechanisms of immune aging. In addition to discovering new therapeutic targets, the findings underscore the value of transcription studies and network analysis to characterize complex biological processes, and serve as a model to analyze the susceptibility of the elderly to infectious agents. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-022-00286-9.
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spelling pubmed-91581622022-06-02 Altered transcriptional responses in the lungs of aged mice after influenza infection Hernandez, Ana M. Mossman, Jim A. Toapanta, Franklin R. Previte, Dana M. Ross, Ted M. Nau, Gerard J. Immun Ageing Research BACKGROUND: Influenza causes a serious infection in older individuals who are at the highest risk for mortality from this virus. Changes in the immune system with age are well known. This study used transcriptomic analysis to evaluate how aging specifically affects the functional host response to influenza in the lung. Adult (12–16 weeks) and aged (72–76 weeks) mice were infected with influenza and lungs were processed for RNA analysis. RESULTS: Older mice demonstrated a delayed anti-viral response on the level of transcription compared to adults, similar to the immunologic responses measured in prior work. The transcriptional differences, however, were evident days before observable differences in the protein responses described previously. The transcriptome response to influenza in aged mice was dominated by immunoglobulin genes and B cell markers compared to adult animals, suggesting immune dysregulation. Despite these differences, both groups of mice had highly similar transcriptional responses involving non-immune genes one day after inoculation and T cell genes during resolution. CONCLUSIONS: These results define a delayed and dysregulated immune response in the lungs of aged mice infected with influenza. The findings implicate B cells and immunoglobulins as markers or mechanisms of immune aging. In addition to discovering new therapeutic targets, the findings underscore the value of transcription studies and network analysis to characterize complex biological processes, and serve as a model to analyze the susceptibility of the elderly to infectious agents. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-022-00286-9. BioMed Central 2022-06-01 /pmc/articles/PMC9158162/ /pubmed/35650631 http://dx.doi.org/10.1186/s12979-022-00286-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hernandez, Ana M.
Mossman, Jim A.
Toapanta, Franklin R.
Previte, Dana M.
Ross, Ted M.
Nau, Gerard J.
Altered transcriptional responses in the lungs of aged mice after influenza infection
title Altered transcriptional responses in the lungs of aged mice after influenza infection
title_full Altered transcriptional responses in the lungs of aged mice after influenza infection
title_fullStr Altered transcriptional responses in the lungs of aged mice after influenza infection
title_full_unstemmed Altered transcriptional responses in the lungs of aged mice after influenza infection
title_short Altered transcriptional responses in the lungs of aged mice after influenza infection
title_sort altered transcriptional responses in the lungs of aged mice after influenza infection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158162/
https://www.ncbi.nlm.nih.gov/pubmed/35650631
http://dx.doi.org/10.1186/s12979-022-00286-9
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