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

被引：63

作者：

Lian, Qizhou ^{[1
,2
,3
]}

Zhang, Kui ^{[4
,5
]}

Zhang, Zhao ^{[2
,3
]}

Duan, Fuyu ^{[1
]}

Guo, Liyan ^{[1
]}

Luo, Weiren ^{[6
]}

Mok, Bobo Wing-Yee ^{[7
,8
]}

Thakur, Abhimanyu ^{[4
,5
]}

Ke, Xiaoshan ^{[4
,5
]}

Motallebnejad, Pedram ^{[4
,5
]}

Nicolaescu, Vlad ^{[9
]}

Chen, Jonathan ^{[10
]}

Ma, Chui Yan ^{[1
]}

Zhou, Xiaoya ^{[2
,3
]}

Han, Shuo ^{[11
]}

Han, Teng ^{[12
]}

Zhang, Wei ^{[13
]}

Tan, Adrian Y. ^{[13
]}

Zhang, Tuo ^{[13
]}

Wang, Xing ^{[13
]}

Xu, Dong ^{[13
]}

Xiang, Jenny ^{[13
]}

Xu, Aimin ^{[14
]}

Liao, Can ^{[1
]}

Huang, Fang-Ping ^{[15
]}

Chen, Ya-Wen ^{[16
,17
]}

Na, Jie ^{[18
]}

Randall, Glenn ^{[9
]}

Tse, Hung-fat ^{[2
,3
]}

Chen, Zhiwei ^{[19
,20
]}

Chen, Yin ^{[21
]}

Chen, Huanhuan Joyce ^{[4
,5
]}

机构：

[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

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

国家重点研发计划;

关键词：

COVID-19; LUNG;

D O I：

10.1038/s41467-022-29731-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 52 条

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