The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi.

Chan, LLY; Anderson, DE; Cheng, HS; Ivan, FX; Chen, S; Kang, AEZ; Foo, R; Gamage, AM; Tiew, PY; Koh, MS; Lee, KCH; Nichol, K; Pathinayake, PS; Chan, YL; Yeo, TW; Oliver, BG; Wark, PAB; Liu, L; Tan, NS; Wang, L-F; Chotirmall, SH

The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi.

Chan, LLY Anderson, DE Cheng, HS Ivan, FX Chen, S Kang, AEZ Foo, R Gamage, AM Tiew, PY Koh, MS Lee, KCH Nichol, K Pathinayake, PS Chan, YL Yeo, TW Oliver, BG Wark, PAB Liu, L Tan, NS Wang, L-F Chotirmall, SH

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Publisher:: Springer Nature
Publication Type:: Journal Article
Citation:: Nat Commun, 2022, 13, (1), pp. 7635
Issue Date:: 2022-12-10

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Field	Value	Language
dc.contributor.author	Chan, LLY
dc.contributor.author	Anderson, DE
dc.contributor.author	Cheng, HS
dc.contributor.author	Ivan, FX
dc.contributor.author	Chen, S
dc.contributor.author	Kang, AEZ
dc.contributor.author	Foo, R
dc.contributor.author	Gamage, AM
dc.contributor.author	Tiew, PY
dc.contributor.author	Koh, MS
dc.contributor.author	Lee, KCH
dc.contributor.author	Nichol, K
dc.contributor.author	Pathinayake, PS
dc.contributor.author	Chan, YL
dc.contributor.author	Yeo, TW
dc.contributor.author	Oliver, BG
dc.contributor.author	Wark, PAB
dc.contributor.author	Liu, L
dc.contributor.author	Tan, NS
dc.contributor.author	Wang, L-F
dc.contributor.author	Chotirmall, SH
dc.date.accessioned	2023-02-28T04:54:07Z
dc.date.available	2022-11-22
dc.date.available	2023-02-28T04:54:07Z
dc.date.issued	2022-12-10
dc.identifier.citation	Nat Commun, 2022, 13, (1), pp. 7635
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/166565
dc.description.abstract	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.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Nature
dc.relation.ispartof	Nat Commun
dc.relation.isbasedon	10.1038/s41467-022-35253-x
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Humans
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	COVID-19
dc.subject.mesh	Organoids
dc.subject.mesh	Bronchi
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Bronchi
dc.subject.mesh	Organoids
dc.subject.mesh	Humans
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	COVID-19
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	Humans
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	COVID-19
dc.subject.mesh	Organoids
dc.subject.mesh	Bronchi
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Host-Pathogen Interactions
dc.title	The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi.
dc.type	Journal Article
utslib.citation.volume	13
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2023-02-28T04:54:00Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	13
utslib.citation.issue	1

Abstract:

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.

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http://hdl.handle.net/10453/166565