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

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, Xiaoya Zhou, Shuo Han, Teng Han, Wei Zhang, Adrian Y. Tan, Tuo Zhang, Xing Wang, Dong Xu, Jenny Xiang, Aimin Xu, Can Liao, Fang-Ping Huang, Ya-Wen Chen, Jie Na, Glenn Randall, Hung-fat Tse, Zhiwei Chen, Yin Chen and Huanhuan Joyce Chen ()
Additional contact information
Qizhou Lian: Guangzhou Medical University
Kui Zhang: 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
Xiaoshan Ke: the University of Chicago
Pedram Motallebnejad: 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
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

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-29731-5

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