SARS-CoV-2 Impairs Dendritic Cells and Regulates DC-SIGN Gene Expression in Tissues

Abstract

The current spreading coronavirus SARS-CoV-2 is highly infectious and pathogenic. In this study, we screened the gene expression of three host receptors (ACE2, DC-SIGN and L-SIGN) of SARS coronaviruses and dendritic cells (DCs) status in bulk and single cell transcriptomic datasets of upper airway, lung or blood of COVID-19 patients and healthy controls. In COVID-19 patients, DC-SIGN gene expression was interestingly decreased in lung DCs but increased in blood DCs. Within DCs, conventional DCs (cDCs) were depleted while plasmacytoid DCs (pDCs) were augmented in the lungs of mild COVID-19. In severe cases, we identified augmented types of immature DCs (CD22+ or ANXA1+ DCs) with MHCII downregulation. In this study, our observation indicates that DCs in severe cases stimulate innate immune responses but fail to specifically present SARS-CoV-2. It provides insights into the profound modulation of DC function in severe COVID-19.

Identifying factors contributing to increased susceptibility to COVID-19 risk: a systematic review of Mendelian randomization studies

“…Inhibition of IL6 receptor (proxied by lower CRP) 9 , 67 , 68 , 74 and its common signal-transducing receptor subunit, glycoprotein 130 (gp130), 77 higher IL10 receptor beta subunit (IL10RB) 78 and higher IL17 receptor A (IL17RA) 72 were associated with lower risk of COVID-19. There was no evidence supporting the role of protein angiotensin-converting enzyme (ACE), ACE2 and liver/lymph node-specific intercellular adhesion molecule-3-grabbing non-integrin (L-SIGN) in COVID-19 risk, 69 , 70 although positive association of dendritic cell (DC)-SIGN (also known as cluster of differentiation, CD209) in COVID-19 susceptibility and severity was found. 67 , 70 Higher protein expression of family with sequence similarity 3, member D (FAM3D), intercellular adhesion molecule 1 (ICAM1) and sulfhydryl oxidase 2 (QSOX2) and lower protein expression of e-selectin (SELE) were associated with higher COVID-19 risk.…”

“…There was no evidence supporting the role of protein angiotensin-converting enzyme (ACE), ACE2 and liver/lymph node-specific intercellular adhesion molecule-3-grabbing non-integrin (L-SIGN) in COVID-19 risk, 69 , 70 although positive association of dendritic cell (DC)-SIGN (also known as cluster of differentiation, CD209) in COVID-19 susceptibility and severity was found. 67 , 70 Higher protein expression of family with sequence similarity 3, member D (FAM3D), intercellular adhesion molecule 1 (ICAM1) and sulfhydryl oxidase 2 (QSOX2) and lower protein expression of e-selectin (SELE) were associated with higher COVID-19 risk. 67 Extensive tissue-specific gene expression of druggable targets has also been explored 71 , 73 , 75 , 76 , 78 in which gene expression of OAS1, 78 ACE2, 71 IL10RB 71 and interferon (IFN) alpha receptor 2 (IFNAR2) 71 , 73 , 75 , 76 across several tissues was related to COVID-19 risk ( Supplementary Table S1 , available as Supplementary data at IJE online).…”

Depletion and Dysfunction of Dendritic Cells: Understanding SARS-CoV-2 Infection

“…Michel et al confirm the important role of DC-SIGN in the Trojan Horse model of DCs during SARS-CoV-2 infection (87). They think that SARS-CoV-2 adheres to the surface of DCs through DC-SIGN and secondly present SARS-CoV-2 to susceptible cells in the process recognized as trans-infection which relies on the characteristics of DCs' migration (87). Intriguingly, the DC-SIGN gene expression is interestingly decreased in lung DCs but increased in circulation DCs which would undoubtedly increase the amount of SARS-CoV-2 carried by DCs and enhance its global transmission ability (88).…”

“…The DC-SIGN/L-SIGN may be an alternative receptor, due to the fact that ACE2deficient endothelial cells but not DC-SIGNR-deficient endothelial cells allow SARS-CoV-2 entry (85,86). Michel et al confirm the important role of DC-SIGN in the Trojan Horse model of DCs during SARS-CoV-2 infection (87). They think that SARS-CoV-2 adheres to the surface of DCs through DC-SIGN and secondly present SARS-CoV-2 to susceptible cells in the process recognized as trans-infection which relies on the characteristics of DCs' migration (87).…”

Glycans as a key factor in self and nonself discrimination: impact on the breach of immune tolerance

“…On the contrary, other studies describe that DC‐SIGN acts as a receptor for SARS‐CoV‐2, mediating its entry into human tissues [66‐68]. Of note, an increased expression of DC‐SIGN was observed in severe COVID‐19 patients, associated with higher production of pro‐inflammatory cytokines [63,69]. Furthermore, spike glycans have also been described to be recognized by other C‐type lectins, such as MGL, being associated with COVID‐19 severity [63].…”