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

Author

Listed:
  • Louisa L. Y. Chan

    (Nanyang Technological University)

  • Danielle E. Anderson

    (Duke-NUS Medical School)

  • Hong Sheng Cheng

    (Nanyang Technological University)

  • Fransiskus Xaverius Ivan

    (Nanyang Technological University)

  • Si Chen

    (Nanyang Technological University)

  • Adrian E. Z. Kang

    (Duke-NUS Medical School)

  • Randy Foo

    (Duke-NUS Medical School)

  • Akshamal M. Gamage

    (Duke-NUS Medical School)

  • Pei Yee Tiew

    (Nanyang Technological University
    Singapore General Hospital
    Duke-NUS Medical School)

  • Mariko Siyue Koh

    (Singapore General Hospital
    Duke-NUS Medical School)

  • Ken Cheah Hooi Lee

    (Singapore General Hospital
    Duke-NUS Medical School)

  • Kristy Nichol

    (University of Newcastle)

  • Prabuddha S. Pathinayake

    (University of Newcastle)

  • Yik Lung Chan

    (University of Technology Sydney)

  • Tsin Wen Yeo

    (Nanyang Technological University
    National Centre for Infectious Diseases)

  • Brian G. Oliver

    (University of Technology Sydney
    The University of Sydney)

  • Peter A. B. Wark

    (University of Newcastle
    John Hunter Hospital)

  • Linbo Liu

    (Nanyang Technological University
    Nanyang Technological University)

  • Nguan Soon Tan

    (Nanyang Technological University
    Nanyang Technological University)

  • Lin-Fa Wang

    (Duke-NUS Medical School
    Singhealth Duke-NUS Global Health Institute)

  • Sanjay H. Chotirmall

    (Nanyang Technological University
    Tan Tock Seng Hospital)

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.

Suggested Citation

  • Louisa L. Y. Chan & Danielle E. Anderson & Hong Sheng Cheng & Fransiskus Xaverius Ivan & Si Chen & Adrian E. Z. Kang & Randy Foo & Akshamal M. Gamage & Pei Yee Tiew & Mariko Siyue Koh & Ken Cheah Hooi, 2022. "The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35253-x
    DOI: 10.1038/s41467-022-35253-x
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    References listed on IDEAS

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    Cited by:

    1. Gang Liu & Tatt Jhong Haw & Malcolm R. Starkey & Ashleigh M. Philp & Stelios Pavlidis & Christina Nalkurthi & Prema M. Nair & Henry M. Gomez & Irwan Hanish & Alan CY. Hsu & Elinor Hortle & Sophie Pick, 2023. "TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase," Nature Communications, Nature, vol. 14(1), pages 1-24, December.

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