Publication
The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi
Publisher:
Springer Science and Business Media LLC
Date:
10-12-2022
DOI:
10.1038/S41467-022-35253-X
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 in idual level are lacking. Here, we describe the establishment of nasopharyngeal and bronchial organoids from healthy in iduals and COPD that recapitulate disease at the in idual 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 in idual level and is amenable to the study of host-pathogen interaction and emerging infectious disease.