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Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model.
Lian, Qizhou; Zhang, Kui; Zhang, Zhao; Duan, Fuyu; Guo, Liyan; Luo, Weiren; Mok, Bobo Wing-Yee; Thakur, Abhimanyu; Ke, Xiaoshan; Motallebnejad, Pedram; Nicolaescu, Vlad; Chen, Jonathan; Ma, Chui Yan; Zhou, Xiaoya; Han, Shuo; Han, Teng; Zhang, Wei; Tan, Adrian Y; Zhang, Tuo; Wang, Xing; Xu, Dong; Xiang, Jenny; Xu, Aimin; Liao, Can; Huang, Fang-Ping; Chen, Ya-Wen; Na, Jie; Randall, Glenn; Tse, Hung-Fat; Chen, Zhiwei; Chen, Yin; Chen, Huanhuan Joyce.
  • Lian Q; Cord Blood Bank Center, Cord Blood Bank, Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. qzlian@hku.hk.
  • Zhang K; HKUMed Laboratory of Cellular Therapeutics, and Department of Medicine, the University of Hong Kong, Hong Kong SAR, China. qzlian@hku.hk.
  • Zhang Z; The Pritzker School of Molecular Engineering, the University of Chicago, Chicago, IL, 60637, USA.
  • Duan F; The Ben May Department for Cancer Research, the University of Chicago, Chicago, IL, 60637, USA.
  • Guo L; HKUMed Laboratory of Cellular Therapeutics, and Department of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Luo W; Cord Blood Bank Center, Cord Blood Bank, Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Mok BW; Cord Blood Bank Center, Cord Blood Bank, Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Thakur A; Department of Pathology, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen Third People's Hospital, National Clinical Research Centre for Infectious Diseases, Shenzhen, China.
  • Ke X; Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
  • Motallebnejad P; The Pritzker School of Molecular Engineering, the University of Chicago, Chicago, IL, 60637, USA.
  • Nicolaescu V; The Ben May Department for Cancer Research, the University of Chicago, Chicago, IL, 60637, USA.
  • Chen J; The Pritzker School of Molecular Engineering, the University of Chicago, Chicago, IL, 60637, USA.
  • Ma CY; The Ben May Department for Cancer Research, the University of Chicago, Chicago, IL, 60637, USA.
  • Zhou X; The Pritzker School of Molecular Engineering, the University of Chicago, Chicago, IL, 60637, USA.
  • Han S; The Ben May Department for Cancer Research, the University of Chicago, Chicago, IL, 60637, USA.
  • Han T; Microbiology, Biosciences Division, the University of Chicago, Chicago, IL, 60637, USA.
  • Zhang W; McCormick School of Engineering, Northwestern University, Chicago, IL, USA.
  • Tan AY; Cord Blood Bank Center, Cord Blood Bank, Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Zhang T; HKUMed Laboratory of Cellular Therapeutics, and Department of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Wang X; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
  • Xu D; Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, 10021, USA.
  • Xiang J; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY, 10065, USA.
  • Xu A; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY, 10065, USA.
  • Liao C; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY, 10065, USA.
  • Huang FP; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY, 10065, USA.
  • Chen YW; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY, 10065, USA.
  • Na J; Genomic Resource Core Facility, Weill Cornell Medicine, New York, NY, 10065, USA.
  • Randall G; State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
  • Tse HF; Cord Blood Bank Center, Cord Blood Bank, Guangzhou Institute of Eugenics and Perinatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Chen Z; Institute for Advanced Study (IAS), Shenzhen University, Shenzhen, China.
  • Chen Y; Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Chen HJ; Department of Cell, Developmental, and Regenerative Biology, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Nat Commun ; 13(1): 2028, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1805608
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pluripotent Stem Cells / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-29731-5

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pluripotent Stem Cells / COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-29731-5