Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
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
_version_ 1783255284666335232
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
work_keys_str_mv AT finokristink sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT yanglinlin sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT silveyrapatricia sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT husanmei sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT umsteadtoddm sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT diangelosusan sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT halsteadescott sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT coopertimothyk sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT abrahamthomas sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT takahashiyoshinori sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT zhouzhixiang sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT wanghonggang sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection
AT chroneoszissisc sh3glb2endophilinb2regulateslunghomeostasisandrecoveryfromsevereinfluenzaavirusinfection