tetano
Editor, Senior Moderator
J Infect Dis
. 2020 Jun 21;jiaa356.
doi: 10.1093/infdis/jiaa356. Online ahead of print.
Attenuated Interferon and Pro-Inflammatory Response in SARS-CoV-2-infected Human Dendritic Cells Is Associated With Viral Antagonism of STAT1 Phosphorylation
Dong Yang[SUP] 1 2 [/SUP], Hin Chu[SUP] 1 2 [/SUP], Yuxin Hou[SUP] 1 2 [/SUP], Yue Chai[SUP] 1 2 [/SUP], Huiping Shuai[SUP] 1 2 [/SUP], Andrew Chak-Yiu Lee[SUP] 1 2 [/SUP], Xi Zhang[SUP] 1 2 [/SUP], Yixin Wang[SUP] 1 2 [/SUP], Bingjie Hu[SUP] 1 2 [/SUP], Xiner Huang[SUP] 1 2 [/SUP], Terrence Tsz-Tai Yuen[SUP] 1 2 [/SUP], Jian-Piao Cai[SUP] 1 2 [/SUP], Jie Zhou[SUP] 1 2 [/SUP], Shuofeng Yuan[SUP] 1 2 [/SUP], Anna Jinxia Zhang[SUP] 1 2 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 3 4 5 6 [/SUP], Kwok-Yung Yuen[SUP] 1 2 3 4 5 6 [/SUP]
Affiliations
Abstract
Clinical manifestations of COVID-19 vary from asymptomatic virus shedding, non-specific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells and macrophages are sentinel cells for innate and adaptive immunity that affect the pathogenesis of SARS and MERS. However, the interplay between SARS-CoV-2 and these cell types remains unknown. Herein, we investigated the infection and host response of monocyte-derived dendritic cells (moDCs) and macrophages (MDMs) infected by SARS-CoV-2. We demonstrated that moDCs and MDMs were permissive to SARS-CoV-2 infection and protein expression but did not support productive virus replication. Importantly, SARS-CoV-2 launched an attenuated interferon response in both cell types. Additionally, SARS-CoV-2 triggered significant pro-inflammatory cytokine/chemokine expression in MDMs but not in moDCs. Further investigations suggested that this attenuated immune response to SARS-CoV-2 in moDCs was associated with viral antagonism of STAT1 phosphorylation. These findings on pathogenesis may explain the mild and insidious course of COVID-19 till late deterioration.
Keywords: COVID-19; MDMs; SARS-CoV-2; coronavirus; dendritic cells; macrophages; moDCs.
. 2020 Jun 21;jiaa356.
doi: 10.1093/infdis/jiaa356. Online ahead of print.
Attenuated Interferon and Pro-Inflammatory Response in SARS-CoV-2-infected Human Dendritic Cells Is Associated With Viral Antagonism of STAT1 Phosphorylation
Dong Yang[SUP] 1 2 [/SUP], Hin Chu[SUP] 1 2 [/SUP], Yuxin Hou[SUP] 1 2 [/SUP], Yue Chai[SUP] 1 2 [/SUP], Huiping Shuai[SUP] 1 2 [/SUP], Andrew Chak-Yiu Lee[SUP] 1 2 [/SUP], Xi Zhang[SUP] 1 2 [/SUP], Yixin Wang[SUP] 1 2 [/SUP], Bingjie Hu[SUP] 1 2 [/SUP], Xiner Huang[SUP] 1 2 [/SUP], Terrence Tsz-Tai Yuen[SUP] 1 2 [/SUP], Jian-Piao Cai[SUP] 1 2 [/SUP], Jie Zhou[SUP] 1 2 [/SUP], Shuofeng Yuan[SUP] 1 2 [/SUP], Anna Jinxia Zhang[SUP] 1 2 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 3 4 5 6 [/SUP], Kwok-Yung Yuen[SUP] 1 2 3 4 5 6 [/SUP]
Affiliations
- PMID: 32563187
- DOI: 10.1093/infdis/jiaa356
Abstract
Clinical manifestations of COVID-19 vary from asymptomatic virus shedding, non-specific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells and macrophages are sentinel cells for innate and adaptive immunity that affect the pathogenesis of SARS and MERS. However, the interplay between SARS-CoV-2 and these cell types remains unknown. Herein, we investigated the infection and host response of monocyte-derived dendritic cells (moDCs) and macrophages (MDMs) infected by SARS-CoV-2. We demonstrated that moDCs and MDMs were permissive to SARS-CoV-2 infection and protein expression but did not support productive virus replication. Importantly, SARS-CoV-2 launched an attenuated interferon response in both cell types. Additionally, SARS-CoV-2 triggered significant pro-inflammatory cytokine/chemokine expression in MDMs but not in moDCs. Further investigations suggested that this attenuated immune response to SARS-CoV-2 in moDCs was associated with viral antagonism of STAT1 phosphorylation. These findings on pathogenesis may explain the mild and insidious course of COVID-19 till late deterioration.
Keywords: COVID-19; MDMs; SARS-CoV-2; coronavirus; dendritic cells; macrophages; moDCs.