Attenuated interferon and pro-inflammatory response in SARS-CoV-2-infected human dendritic cells is associated with viral antagonism of STAT1 phosphorylation

Yang, Dong; Chu, Hin; Hou, Yuxin; Chai, Yue; Shuai, Huiping; Lee, Andrew Chak-Yiu; Zhang, Xi; Wang, Yixin; Hu, Bingjie; Huang, Xiner; Yuen, Terrence Tsz-Tai; Cai, Jian-Piao; Zhou, Jie; Yuan, Shuofeng; Zhang, Anna Jinxia; Chan, Jasper Fuk-Woo; Yuen, Kwok-Yung

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.