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

Guoshuai Cai,Prakash Nagarkatti,Xizhi Luo,Mulong Du,Yohan Bossé,Christopher I Amos,Michael L Whitfield,Xiao Michelle Androulakis,Mitzi Nagarkatti,David C Christiani,Fei Qin,Chao Cheng,Helmut Albrecht,Feifei Xiao

doi:10.3390/ijms22179228

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.

Highlights

In 2020, a novel coronavirus SARS-CoV-2 has been spreading as a pandemic infection.SARS-CoV-2 is highly infectious and pathogenic through human-to-human transmission and causes severe Coronavirus Disease 2019 (COVID-19) [1]
In the metagenomic generation sequencing data from nasopharynx/pharynx samples of 197 patients with acute respiratory illnesses (ARIs), we found gene expression of ACE2 (p = 3.9 × 10−10 ) and dendritic cells (DCs)-SIGN (p = 0.048) were significantly higher with the SARS-CoV-2 infection (Supplementary Figure S1)
In SARS-CoV-2 ARIs, the gene expression of ACE2, CD80, CD86, CD83, IFN-γ, FCER1G and IgG Fc receptors (FcRs) were positively associated with the viral load of SARS-CoV-2 (Figure 2A, Supplementary Figure S1), while no significant associations were observed in HLA genes

Summary

Introduction

SARS-CoV-2 is highly infectious and pathogenic through human-to-human transmission and causes severe Coronavirus Disease 2019 (COVID-19) [1]. 80% homology of genome [2] They belong to the same β-genus of coronavirus with similar receptor-binding domain (RBD) structures [3] and cause similar clinical symptoms such as acute respiratory response [4]. For SARS-CoV, three receptors including ACE2, DC-SIGN and L-SIGN (gene symbols ACE2, CD209 and CLEC4M, respectively) have been found to be involved in the pathogenicity [5,6,7], among which ACE2 has been quickly confirmed to be the receptor for SARS-CoV-2 [2]. DC-SIGN and L-SIGN have been considered as potential receptors for SARS-CoV-2 [8,9]. The associations between DC-SIGN/L-SIGN expression and SARS-CoV-2 infection and its phenotypes were not evaluated yet

Methods

Results

Conclusion