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- Title
Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model.
- Authors
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
- 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. 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.
- Subjects
MACROPHAGES; PLURIPOTENT stem cells; SARS-CoV-2; HUMAN stem cells; COVID-19; VIRUS diseases; IMMUNE response
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-29731-5