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Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model

Author

Listed:
  • Qizhou Lian

    (Guangzhou Medical University
    the University of Hong Kong)

  • Kui Zhang

    (the University of Chicago
    the University of Chicago)

  • Zhao Zhang

    (the University of Hong Kong)

  • Fuyu Duan

    (Guangzhou Medical University)

  • Liyan Guo

    (Guangzhou Medical University)

  • Weiren Luo

    (The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen Third People’s Hospital, National Clinical Research Centre for Infectious Diseases)

  • Bobo Wing-Yee Mok

    (The University of Hong Kong)

  • Abhimanyu Thakur

    (the University of Chicago
    the University of Chicago)

  • Xiaoshan Ke

    (the University of Chicago
    the University of Chicago)

  • Pedram Motallebnejad

    (the University of Chicago
    the University of Chicago)

  • Vlad Nicolaescu

    (the University of Chicago)

  • Jonathan Chen

    (Northwestern University)

  • Chui Yan Ma

    (Guangzhou Medical University)

  • Xiaoya Zhou

    (the University of Hong Kong)

  • Shuo Han

    (The University of Hong Kong)

  • Teng Han

    (Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine)

  • Wei Zhang

    (Genomic Resource Core Facility, Weill Cornell Medicine)

  • Adrian Y. Tan

    (Genomic Resource Core Facility, Weill Cornell Medicine)

  • Tuo Zhang

    (Genomic Resource Core Facility, Weill Cornell Medicine)

  • Xing Wang

    (Genomic Resource Core Facility, Weill Cornell Medicine)

  • Dong Xu

    (Genomic Resource Core Facility, Weill Cornell Medicine)

  • Jenny Xiang

    (Genomic Resource Core Facility, Weill Cornell Medicine)

  • Aimin Xu

    (The University of Hong Kong)

  • Can Liao

    (Guangzhou Medical University)

  • Fang-Ping Huang

    (Shenzhen University)

  • Ya-Wen Chen

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Jie Na

    (Tsinghua University)

  • Glenn Randall

    (the University of Chicago)

  • Hung-fat Tse

    (the University of Hong Kong)

  • Zhiwei Chen

    (The University of Hong Kong)

  • Yin Chen

    (University of Arizona)

  • Huanhuan Joyce Chen

    (the University of Chicago
    the University of Chicago)

Abstract

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19), with macrophages as one of the main cell types involved. It is urgent to understand the interactions among permissive cells, macrophages, and the SARS-CoV-2 virus, thereby offering important insights into effective therapeutic strategies. Here, we establish a lung and macrophage co-culture system derived from human pluripotent stem cells (hPSCs), modeling the host-pathogen interaction in SARS-CoV-2 infection. We find that both classically polarized macrophages (M1) and alternatively polarized macrophages (M2) have inhibitory effects on SARS-CoV-2 infection. However, M1 and non-activated (M0) macrophages, but not M2 macrophages, significantly up-regulate inflammatory factors upon viral infection. Moreover, M1 macrophages suppress the growth and enhance apoptosis of lung cells. Inhibition of viral entry using an ACE2 blocking antibody substantially enhances the activity of M2 macrophages. Our studies indicate differential immune response patterns in distinct macrophage phenotypes, which could lead to a range of COVID-19 disease severity.

Suggested Citation

  • Qizhou Lian & Kui Zhang & Zhao Zhang & Fuyu Duan & Liyan Guo & Weiren Luo & Bobo Wing-Yee Mok & Abhimanyu Thakur & Xiaoshan Ke & Pedram Motallebnejad & Vlad Nicolaescu & Jonathan Chen & Chui Yan Ma & , 2022. "Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29731-5
    DOI: 10.1038/s41467-022-29731-5
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    References listed on IDEAS

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