TY - JOUR
T1 - The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi
AU - Chan, Louisa L.Y.
AU - Anderson, Danielle E.
AU - Cheng, Hong Sheng
AU - Ivan, Fransiskus Xaverius
AU - Chen, Si
AU - Kang, Adrian E.Z.
AU - Foo, Randy
AU - Gamage, Akshamal M.
AU - Tiew, Pei Yee
AU - Koh, Mariko Siyue
AU - Lee, Ken Cheah Hooi
AU - Nichol, Kristy
AU - Pathinayake, Prabuddha S.
AU - Chan, Yik Lung
AU - Yeo, Tsin Wen
AU - Oliver, Brian G.
AU - Wark, Peter A.B.
AU - Liu, Linbo
AU - Tan, Nguan Soon
AU - Wang, Lin Fa
AU - Chotirmall, Sanjay H.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-022-35253-x
DO - 10.1038/s41467-022-35253-x
M3 - Article
C2 - 36496442
AN - SCOPUS:85143695123
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 7635
ER -
