Smoking and SARS-CoV-2 Impair Dendritic Cells and Regulate DC-SIGN Expression in Tissues

Author:

Cai Guoshuai,Bossé Yohan,Du Mulong,Albrecht Helmut,Qin Fei,Yu Xuanxuan,Luo Xizhi,Androulakis Michelle,Zhu Xia,Zhou Jun,Cui Xiang,Yi Changhua,Cheng Chao,Nagarkatti Mitzi,Nagarkatti Prakash,Christiani David,Whitfield Michael,Amos Christopher,Xiao Feifei

Abstract

SummaryThe current spreading novel coronavirus SARS-CoV-2 is highly infectious and pathogenic. In this study, we screened the gene expression of three SARS-CoV-2 host receptors (ACE2, DC-SIGN and L-SIGN) and DC status in bulk and single cell transcriptomic datasets of upper airway, lung or blood of smokers, non-smokers and COVID-19 patients. We found smoking increased DC-SIGN gene expression and inhibited DC maturation and its ability of T cell stimulation. In COVID-19, DC-SIGN gene expression was interestingly decreased in lung DCs but increased in blood DCs. Strikingly, DCs shifted from cDCs to pDCs in COVID-19, but the shift was trapped in an immature stage (CD22+ or ANXA1+ DC) with MHCII downregulation in severe cases. This observation indicates that DCs in severe cases stimulate innate immune responses but fail to specifically recognize SARS-CoV-2. Our study provides insights into smoking effect on COVID-19 risk and the profound modulation of DC function in severe COVID-19.Graphical AbstractHighlightsSmoking upregulates the expression of ACE2 and CD209 and inhibits DC maturation in lungs. SARS-CoV-2 modulates the DCs proportion and CD209 expression differently in lung and blood.Severe infection is characterized by DCs less capable of maturation, antigen presentation and MHCII expression.DCs shift from cDCs to pDCs with SARS-CoV-2 infection but are trapped in an immature stage in severe cases.

Publisher

Cold Spring Harbor Laboratory

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