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Single-cell transcriptome of bronchoalveolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets

Author

Listed:
  • Jeong Seok Lee

    (GENOME INSIGHT Inc.)

  • June-Young Koh

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Kijong Yi

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Young-Il Kim

    (Chungbuk National University)

  • Su-Jin Park

    (Chungbuk National University
    Gyeongsang National University)

  • Eun-Ha Kim

    (Chungbuk National University)

  • Se-Mi Kim

    (Chungbuk National University)

  • Sung Ho Park

    (Ulsan National Institute of Science & Technology (UNIST))

  • Young Seok Ju

    (GENOME INSIGHT Inc.
    Korea Advanced Institute of Science and Technology (KAIST)
    The Center for Epidemic Preparedness, KAIST Institute, KAIST)

  • Young Ki Choi

    (Chungbuk National University
    Korea Virus Research Institute, Institute for Basic Science (IBS))

  • Su-Hyung Park

    (Korea Advanced Institute of Science and Technology (KAIST)
    The Center for Epidemic Preparedness, KAIST Institute, KAIST)

Abstract

Few studies have used a longitudinal approach to describe the immune response to SARS-CoV-2 infection. Here, we perform single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment shows distinct changes in cell proportions and characteristics compared to uninfected control, at 2 and 5 days post-infection (dpi). Macrophages are classified into 10 distinct subpopulations with transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, notably at 2 dpi. Moreover, trajectory analysis reveals gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identifies a macrophage subpopulation that has rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we find that M1 or M2 macrophages show distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection.

Suggested Citation

  • Jeong Seok Lee & June-Young Koh & Kijong Yi & Young-Il Kim & Su-Jin Park & Eun-Ha Kim & Se-Mi Kim & Sung Ho Park & Young Seok Ju & Young Ki Choi & Su-Hyung Park, 2021. "Single-cell transcriptome of bronchoalveolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24807-0
    DOI: 10.1038/s41467-021-24807-0
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    Cited by:

    1. Sara Sunshine & Andreas S. Puschnik & Joseph M. Replogle & Matthew T. Laurie & Jamin Liu & Beth Shoshana Zha & James K. Nuñez & Janie R. Byrum & Aidan H. McMorrow & Matthew B. Frieman & Juliane Winkle, 2023. "Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Dhiraj K. Singh & Ekaterina Aladyeva & Shibali Das & Bindu Singh & Ekaterina Esaulova & Amanda Swain & Mushtaq Ahmed & Journey Cole & Chivonne Moodley & Smriti Mehra & Larry S. Schlesinger & Maxim N. , 2022. "Myeloid cell interferon responses correlate with clearance of SARS-CoV-2," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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