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The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi
Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9735280/ https://www.ncbi.nlm.nih.gov/pubmed/36496442 http://dx.doi.org/10.1038/s41467-022-35253-x |
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author | Chan, Louisa L. Y. Anderson, Danielle E. Cheng, Hong Sheng Ivan, Fransiskus Xaverius Chen, Si Kang, Adrian E. Z. Foo, Randy Gamage, Akshamal M. Tiew, Pei Yee Koh, Mariko Siyue Lee, Ken Cheah Hooi Nichol, Kristy Pathinayake, Prabuddha S. Chan, Yik Lung Yeo, Tsin Wen Oliver, Brian G. Wark, Peter A. B. Liu, Linbo Tan, Nguan Soon Wang, Lin-Fa Chotirmall, Sanjay H. |
author_facet | Chan, Louisa L. Y. Anderson, Danielle E. Cheng, Hong Sheng Ivan, Fransiskus Xaverius Chen, Si Kang, Adrian E. Z. Foo, Randy Gamage, Akshamal M. Tiew, Pei Yee Koh, Mariko Siyue Lee, Ken Cheah Hooi Nichol, Kristy Pathinayake, Prabuddha S. Chan, Yik Lung Yeo, Tsin Wen Oliver, Brian G. Wark, Peter A. B. Liu, Linbo Tan, Nguan Soon Wang, Lin-Fa Chotirmall, Sanjay H. |
author_sort | Chan, Louisa L. Y. |
collection | PubMed |
description | Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy individuals and COPD that recapitulate disease at the individual level. In contrast to healthy organoids, goblet cell hyperplasia and reduced ciliary beat frequency were observed in COPD organoids, hallmark features of the disease. Single-cell transcriptomics uncovered evidence for altered cellular differentiation trajectories in COPD organoids. SARS-CoV-2 infection of COPD organoids revealed more productive replication in bronchi, the key site of infection in severe COVID-19. Viral and bacterial exposure of organoids induced greater pro-inflammatory responses in COPD organoids. In summary, we present an organoid model that recapitulates the in vivo physiological lung microenvironment at the individual level and is amenable to the study of host-pathogen interaction and emerging infectious disease. |
format | Online Article Text |
id | pubmed-9735280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97352802022-12-12 The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi Chan, Louisa L. Y. Anderson, Danielle E. Cheng, Hong Sheng Ivan, Fransiskus Xaverius Chen, Si Kang, Adrian E. Z. Foo, Randy Gamage, Akshamal M. Tiew, Pei Yee Koh, Mariko Siyue Lee, Ken Cheah Hooi Nichol, Kristy Pathinayake, Prabuddha S. Chan, Yik Lung Yeo, Tsin Wen Oliver, Brian G. Wark, Peter A. B. Liu, Linbo Tan, Nguan Soon Wang, Lin-Fa Chotirmall, Sanjay H. Nat Commun Article Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at the individual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy individuals and COPD that recapitulate disease at the individual level. In contrast to healthy organoids, goblet cell hyperplasia and reduced ciliary beat frequency were observed in COPD organoids, hallmark features of the disease. Single-cell transcriptomics uncovered evidence for altered cellular differentiation trajectories in COPD organoids. SARS-CoV-2 infection of COPD organoids revealed more productive replication in bronchi, the key site of infection in severe COVID-19. Viral and bacterial exposure of organoids induced greater pro-inflammatory responses in COPD organoids. In summary, we present an organoid model that recapitulates the in vivo physiological lung microenvironment at the individual level and is amenable to the study of host-pathogen interaction and emerging infectious disease. Nature Publishing Group UK 2022-12-10 /pmc/articles/PMC9735280/ /pubmed/36496442 http://dx.doi.org/10.1038/s41467-022-35253-x 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 Chan, Louisa L. Y. Anderson, Danielle E. Cheng, Hong Sheng Ivan, Fransiskus Xaverius Chen, Si Kang, Adrian E. Z. Foo, Randy Gamage, Akshamal M. Tiew, Pei Yee Koh, Mariko Siyue Lee, Ken Cheah Hooi Nichol, Kristy Pathinayake, Prabuddha S. Chan, Yik Lung Yeo, Tsin Wen Oliver, Brian G. Wark, Peter A. B. Liu, Linbo Tan, Nguan Soon Wang, Lin-Fa Chotirmall, Sanjay H. The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
title | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
title_full | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
title_fullStr | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
title_full_unstemmed | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
title_short | The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi |
title_sort | establishment of copd organoids to study host-pathogen interaction reveals enhanced viral fitness of sars-cov-2 in bronchi |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9735280/ https://www.ncbi.nlm.nih.gov/pubmed/36496442 http://dx.doi.org/10.1038/s41467-022-35253-x |
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