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

Autor: Chan LLY; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. louisa.chanly@ntu.edu.sg., Anderson DE; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore., Cheng HS; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore., Ivan FX; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore., Chen S; School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore, Singapore., Kang AEZ; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore., Foo R; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore., Gamage AM; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore., Tiew PY; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.; Duke-NUS Medical School, Singapore, Singapore., Koh MS; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.; Duke-NUS Medical School, Singapore, Singapore., Lee KCH; Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.; Duke-NUS Medical School, Singapore, Singapore., Nichol K; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia., Pathinayake PS; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia., Chan YL; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia., Yeo TW; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.; National Centre for Infectious Diseases, Singapore, Singapore., Oliver BG; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.; Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, Australia., Wark PAB; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.; Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW, Australia., Liu L; School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore, Singapore.; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore., Tan NS; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, Singapore., Wang LF; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.; Singhealth Duke-NUS Global Health Institute, Singapore, Singapore., Chotirmall SH; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. schotirmall@ntu.edu.sg.; Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore, Singapore. schotirmall@ntu.edu.sg.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Dec 10; Vol. 13 (1), pp. 7635. Date of Electronic Publication: 2022 Dec 10.
DOI: 10.1038/s41467-022-35253-x
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: