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SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection
New influenza A viruses that emerge frequently elicit composite inflammatory responses to both infection and structural damage of alveolar-capillary barrier cells that hinders regeneration of respiratory function. The host factors that relinquish restoration of lung health to enduring lung injury ar...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544693/ https://www.ncbi.nlm.nih.gov/pubmed/28779131 http://dx.doi.org/10.1038/s41598-017-07724-5 |
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author | Fino, Kristin K. Yang, Linlin Silveyra, Patricia Hu, Sanmei Umstead, Todd M. DiAngelo, Susan Halstead, E. Scott Cooper, Timothy K. Abraham, Thomas Takahashi, Yoshinori Zhou, Zhixiang Wang, Hong Gang Chroneos, Zissis C. |
author_facet | Fino, Kristin K. Yang, Linlin Silveyra, Patricia Hu, Sanmei Umstead, Todd M. DiAngelo, Susan Halstead, E. Scott Cooper, Timothy K. Abraham, Thomas Takahashi, Yoshinori Zhou, Zhixiang Wang, Hong Gang Chroneos, Zissis C. |
author_sort | Fino, Kristin K. |
collection | PubMed |
description | New influenza A viruses that emerge frequently elicit composite inflammatory responses to both infection and structural damage of alveolar-capillary barrier cells that hinders regeneration of respiratory function. The host factors that relinquish restoration of lung health to enduring lung injury are insufficiently understood. Here, we investigated the role of endophilin B2 (B2) in susceptibility to severe influenza infection. WT and B2-deficient mice were infected with H1N1 PR8 by intranasal administration and course of influenza pneumonia, inflammatory, and tissue responses were monitored over time. Disruption of B2 enhanced recovery from severe influenza infection as indicated by swift body weight recovery and significantly better survival of endophilin B2-deficient mice compared to WT mice. Compared to WT mice, the B2-deficient lungs exhibited induction of genes that express surfactant proteins, ABCA3, GM-CSF, podoplanin, and caveolin mRNA after 7 days, temporal induction of CCAAT/enhancer binding protein CEBPα, β, and δ mRNAs 3–14 days after infection, and differences in alveolar extracellular matrix integrity and respiratory mechanics. Flow cytometry and gene expression studies demonstrated robust recovery of alveolar macrophages and recruitment of CD4+ lymphocytes in B2-deficient lungs. Targeting of endophilin B2 alleviates adverse effects of IAV infection on respiratory and immune cells enabling restoration of alveolar homeostasis. |
format | Online Article Text |
id | pubmed-5544693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55446932017-08-07 SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection Fino, Kristin K. Yang, Linlin Silveyra, Patricia Hu, Sanmei Umstead, Todd M. DiAngelo, Susan Halstead, E. Scott Cooper, Timothy K. Abraham, Thomas Takahashi, Yoshinori Zhou, Zhixiang Wang, Hong Gang Chroneos, Zissis C. Sci Rep Article New influenza A viruses that emerge frequently elicit composite inflammatory responses to both infection and structural damage of alveolar-capillary barrier cells that hinders regeneration of respiratory function. The host factors that relinquish restoration of lung health to enduring lung injury are insufficiently understood. Here, we investigated the role of endophilin B2 (B2) in susceptibility to severe influenza infection. WT and B2-deficient mice were infected with H1N1 PR8 by intranasal administration and course of influenza pneumonia, inflammatory, and tissue responses were monitored over time. Disruption of B2 enhanced recovery from severe influenza infection as indicated by swift body weight recovery and significantly better survival of endophilin B2-deficient mice compared to WT mice. Compared to WT mice, the B2-deficient lungs exhibited induction of genes that express surfactant proteins, ABCA3, GM-CSF, podoplanin, and caveolin mRNA after 7 days, temporal induction of CCAAT/enhancer binding protein CEBPα, β, and δ mRNAs 3–14 days after infection, and differences in alveolar extracellular matrix integrity and respiratory mechanics. Flow cytometry and gene expression studies demonstrated robust recovery of alveolar macrophages and recruitment of CD4+ lymphocytes in B2-deficient lungs. Targeting of endophilin B2 alleviates adverse effects of IAV infection on respiratory and immune cells enabling restoration of alveolar homeostasis. Nature Publishing Group UK 2017-08-04 /pmc/articles/PMC5544693/ /pubmed/28779131 http://dx.doi.org/10.1038/s41598-017-07724-5 Text en © The Author(s) 2017 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Fino, Kristin K. Yang, Linlin Silveyra, Patricia Hu, Sanmei Umstead, Todd M. DiAngelo, Susan Halstead, E. Scott Cooper, Timothy K. Abraham, Thomas Takahashi, Yoshinori Zhou, Zhixiang Wang, Hong Gang Chroneos, Zissis C. SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection |
title | SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection |
title_full | SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection |
title_fullStr | SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection |
title_full_unstemmed | SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection |
title_short | SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection |
title_sort | sh3glb2/endophilin b2 regulates lung homeostasis and recovery from severe influenza a virus infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544693/ https://www.ncbi.nlm.nih.gov/pubmed/28779131 http://dx.doi.org/10.1038/s41598-017-07724-5 |
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