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Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip

Mechanical breathing motions have a fundamental function in lung development and disease, but little is known about how they contribute to host innate immunity. Here we use a human lung alveolus chip that experiences cyclic breathing-like deformations to investigate whether physical forces influence...

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Autores principales: Bai, Haiqing, Si, Longlong, Jiang, Amanda, Belgur, Chaitra, Zhai, Yunhao, Plebani, Roberto, Oh, Crystal Yuri, Rodas, Melissa, Patil, Aditya, Nurani, Atiq, Gilpin, Sarah E., Powers, Rani K., Goyal, Girija, Prantil-Baun, Rachelle, Ingber, Donald E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993817/
https://www.ncbi.nlm.nih.gov/pubmed/35396513
http://dx.doi.org/10.1038/s41467-022-29562-4
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author Bai, Haiqing
Si, Longlong
Jiang, Amanda
Belgur, Chaitra
Zhai, Yunhao
Plebani, Roberto
Oh, Crystal Yuri
Rodas, Melissa
Patil, Aditya
Nurani, Atiq
Gilpin, Sarah E.
Powers, Rani K.
Goyal, Girija
Prantil-Baun, Rachelle
Ingber, Donald E.
author_facet Bai, Haiqing
Si, Longlong
Jiang, Amanda
Belgur, Chaitra
Zhai, Yunhao
Plebani, Roberto
Oh, Crystal Yuri
Rodas, Melissa
Patil, Aditya
Nurani, Atiq
Gilpin, Sarah E.
Powers, Rani K.
Goyal, Girija
Prantil-Baun, Rachelle
Ingber, Donald E.
author_sort Bai, Haiqing
collection PubMed
description Mechanical breathing motions have a fundamental function in lung development and disease, but little is known about how they contribute to host innate immunity. Here we use a human lung alveolus chip that experiences cyclic breathing-like deformations to investigate whether physical forces influence innate immune responses to viral infection. Influenza H3N2 infection of mechanically active chips induces a cascade of host responses including increased lung permeability, apoptosis, cell regeneration, cytokines production, and recruitment of circulating immune cells. Comparison with static chips reveals that breathing motions suppress viral replication by activating protective innate immune responses in epithelial and endothelial cells, which are mediated in part through activation of the mechanosensitive ion channel TRPV4 and signaling via receptor for advanced glycation end products (RAGE). RAGE inhibitors suppress cytokines induction, while TRPV4 inhibition attenuates both inflammation and viral burden, in infected chips with breathing motions. Therefore, TRPV4 and RAGE may serve as new targets for therapeutic intervention in patients infected with influenza and other potential pandemic viruses that cause life-threatening lung inflammation.
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spelling pubmed-89938172022-04-22 Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip Bai, Haiqing Si, Longlong Jiang, Amanda Belgur, Chaitra Zhai, Yunhao Plebani, Roberto Oh, Crystal Yuri Rodas, Melissa Patil, Aditya Nurani, Atiq Gilpin, Sarah E. Powers, Rani K. Goyal, Girija Prantil-Baun, Rachelle Ingber, Donald E. Nat Commun Article Mechanical breathing motions have a fundamental function in lung development and disease, but little is known about how they contribute to host innate immunity. Here we use a human lung alveolus chip that experiences cyclic breathing-like deformations to investigate whether physical forces influence innate immune responses to viral infection. Influenza H3N2 infection of mechanically active chips induces a cascade of host responses including increased lung permeability, apoptosis, cell regeneration, cytokines production, and recruitment of circulating immune cells. Comparison with static chips reveals that breathing motions suppress viral replication by activating protective innate immune responses in epithelial and endothelial cells, which are mediated in part through activation of the mechanosensitive ion channel TRPV4 and signaling via receptor for advanced glycation end products (RAGE). RAGE inhibitors suppress cytokines induction, while TRPV4 inhibition attenuates both inflammation and viral burden, in infected chips with breathing motions. Therefore, TRPV4 and RAGE may serve as new targets for therapeutic intervention in patients infected with influenza and other potential pandemic viruses that cause life-threatening lung inflammation. Nature Publishing Group UK 2022-04-08 /pmc/articles/PMC8993817/ /pubmed/35396513 http://dx.doi.org/10.1038/s41467-022-29562-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bai, Haiqing
Si, Longlong
Jiang, Amanda
Belgur, Chaitra
Zhai, Yunhao
Plebani, Roberto
Oh, Crystal Yuri
Rodas, Melissa
Patil, Aditya
Nurani, Atiq
Gilpin, Sarah E.
Powers, Rani K.
Goyal, Girija
Prantil-Baun, Rachelle
Ingber, Donald E.
Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip
title Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip
title_full Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip
title_fullStr Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip
title_full_unstemmed Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip
title_short Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip
title_sort mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993817/
https://www.ncbi.nlm.nih.gov/pubmed/35396513
http://dx.doi.org/10.1038/s41467-022-29562-4
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