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

Cai, G.; Bosse, Y.; Du, M.; Albrecht, H.; Qin, F.; Yu, X.; Luo, X.; Androulakis, M.; Zhu, X.; Zhou, J.; Cui, X.; Yi, C.; Cheng, C.; Nagarkatti, M.; Nagarkatti, P.; Christiani, D.; Whitfield, M.; Amos, C.; Xiao, F.

The 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.