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

Lian, Qizhou1,2,3; Zhang, Kui4,5; Zhang, Zhao2,3; Duan, Fuyu1; Guo, Liyan1; Luo, Weiren6; Mok, Bobo Wing-Yee7,8; Thakur, Abhimanyu4,5; Ke, Xiaoshan4,5; Motallebnejad, Pedram4,5; Nicolaescu, Vlad9; Chen, Jonathan10; Ma, Chui Yan1; Zhou, Xiaoya2,3; Han, Shuo11; Han, Teng12; Zhang, Wei13; Tan, Adrian Y.13; Zhang, Tuo13; Wang, Xing13; Xu, Dong13; Xiang, Jenny13; Xu, Aimin14; Liao, Can1; Huang, Fang-Ping15; Chen, Ya-Wen16,17; Na, Jie18; Randall, Glenn9; Tse, Hung-fat2,3; Chen, Zhiwei19,20; Chen, Yin21; Chen, Huanhuan Joyce4,5

2022-04-19

10.1038/s41467-022-29731-5

NATURE COMMUNICATIONS   影响因子和分区

2041-1723

["Model systems to study SARS-CoV-2 infection are required to better understand the immune response. Here the authors use a lung and macrophage co-culture system by differentiation of human pluripotent stem cells to better understand the phenotype and gene expression changes in host lung cells and macrophages after SARS-CoV-2 infection in vitro.","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."]

SCI

英语

NI论文

其他

U.S. National Institute of Health["NCI R00 CA226353-01A1","NCI K99 CA226353-01A1"] ; Hong Kong Health and Medical Research Fund (HMRF), Hong Kong[06172956] ; Start-up Grant for Stem Cell Regenerative Medicine (Guangzhou Women and Children's Medical Centre)[5001-4001010] ; Shenzhen Science and Technology Program[JCYJ20210324114606019] ; Tsinghua University Spring Breeze Fund[2021Z99CFY033] ; National Key R&D Program of China["2019YFA0110001","2017YFA0102802"] ; National Natural Science Grant of China[31970819]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000784997300059

NATURE PORTFOLIO

Web of Science

1.Guangzhou Med Univ, Guangzhou Inst Eugen & Perinatol, Guangzhou Women & Childrens Med Ctr, Cord Blood Bank Ctr,Cord Blood Bank, Guangzhou, Peoples R China
2.Univ Hong Kong, HKUMed Lab Cellular Therapeut, Hong Kong Sar, Peoples R China
3.Univ Hong Kong, Dept Med, Hong Kong Sar, Peoples R China
4.Univ Chicago, Pritzker Sch Mol Engn, Chicago, IL 60637 USA
5.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Dept Pathol,Affiliated Hosp 2, Shenzhen, Peoples R China
7.Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Hong Kong Sar, Peoples R China
8.Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, Hong Kong Sar, Peoples R China
9.Univ Chicago, Biosci Div, Microbiol, Chicago, IL 60637 USA
10.Northwestern Univ, McCormick Sch Engn, Chicago, IL USA
11.Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong Sar, Peoples R China
12.Weill Cornell Med, Dept Med, Sandra & Edward Meyer Canc Ctr, New York, NY 10021 USA
13.Weill Cornell Med, Genom Resource Core Facil, New York, NY 10065 USA
14.Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Pharmaceut Biotechnol, Hong Kong Sar, Peoples R China
15.Shenzhen Univ, Inst Adv Study IAS, Shenzhen, Peoples R China
16.Icahn Sch Med Mt Sinai, Dept Otolaryngol, New York, NY USA
17.Icahn Sch Med Mt Sinai, Black Family Stem Cell Inst, Dept Cell Dev & Regenerat Biol, New York, NY 10029 USA
18.Tsinghua Univ, Sch Med, Beijing, Peoples R China
19.Univ Hong Kong, AIDS Inst, Hong Kong, Peoples R China
20.Univ Hong Kong, Dept Microbiol, State Key Lab Emergent Infect Dis, Hong Kong, Peoples R China
21.Univ Arizona, Sch Pharm, Dept Pharmacol & Toxicol, Tucson, AZ USA

Lian, Qizhou,Zhang, Kui,Zhang, Zhao,et al. Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model[J]. NATURE COMMUNICATIONS,2022,13(1).

Lian, Qizhou.,Zhang, Kui.,Zhang, Zhao.,Duan, Fuyu.,Guo, Liyan.,...&Chen, Huanhuan Joyce.(2022).Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model.NATURE COMMUNICATIONS,13(1).

Lian, Qizhou,et al."Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model".NATURE COMMUNICATIONS 13.1(2022).