TY - JOUR
T1 - Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model
AU - Lian, Qizhou
AU - Zhang, Kui
AU - Zhang, Zhao
AU - Duan, Fuyu
AU - Guo, Liyan
AU - Luo, Weiren
AU - Mok, Bobo Wing Yee
AU - Thakur, Abhimanyu
AU - Ke, Xiaoshan
AU - Motallebnejad, Pedram
AU - Nicolaescu, Vlad
AU - Chen, Jonathan
AU - Ma, Chui Yan
AU - Zhou, Xiaoya
AU - Han, Shuo
AU - Han, Teng
AU - Zhang, Wei
AU - Tan, Adrian Y.
AU - Zhang, Tuo
AU - Wang, Xing
AU - Xu, Dong
AU - Xiang, Jenny
AU - Xu, Aimin
AU - Liao, Can
AU - Huang, Fang Ping
AU - Chen, Ya Wen
AU - Na, Jie
AU - Randall, Glenn
AU - Tse, Hung fat
AU - Chen, Zhiwei
AU - Chen, Yin
AU - Chen, Huanhuan Joyce
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-29731-5
DO - 10.1038/s41467-022-29731-5
M3 - Article
C2 - 35440562
AN - SCOPUS:85128420766
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2028
ER -