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

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

doi:10.3390/ijms22179228

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

Int J Mol Sci. 2021 Aug 26;22(17):9228. doi: 10.3390/ijms22179228.

Authors

Guoshuai Cai¹, Mulong Du^{2

3}, Yohan Bossé⁴, Helmut Albrecht⁵, Fei Qin⁶, Xizhi Luo⁶, Xiao Michelle Androulakis^{7

8}, Chao Cheng^{9

10}, Mitzi Nagarkatti¹¹, Prakash Nagarkatti¹¹, David C Christiani^{2

12}, Michael L Whitfield¹³, Christopher I Amos^{9

10}, Feifei Xiao⁶

Affiliations

¹ Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
² Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
³ Center for Global Health, Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
⁴ Department of Molecular Medicine, Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Laval University, Quebec City, QC G1V 4G5, Canada.
⁵ Prisma Health Medical Group, Department of Internal Medicine, University of South Carolina, Columbia, SC 29208, USA.
⁶ Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA.
⁷ Neurology, Columbia VA Health System, Columbia, SC 29209, USA.
⁸ Department of Neurology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA.
⁹ Department of Medicine, Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX 77030, USA.
¹⁰ Dan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77054, USA.
¹¹ Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA.
¹² Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
¹³ Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.

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.

Keywords: ACE2; COVID-19; DC-SIGN; L-SIGN; dendritic cells.

MeSH terms

Angiotensin-Converting Enzyme 2 / genetics
Angiotensin-Converting Enzyme 2 / metabolism
COVID-19 / diagnosis
COVID-19 / immunology*
COVID-19 / pathology
COVID-19 / virology
Cell Adhesion Molecules / genetics*
Cell Adhesion Molecules / metabolism
Datasets as Topic
Dendritic Cells / immunology*
Dendritic Cells / metabolism
Gene Expression Regulation / immunology*
Genome-Wide Association Study
Host-Pathogen Interactions / genetics
Host-Pathogen Interactions / immunology
Humans
Immunity, Innate
Lectins, C-Type / genetics*
Lectins, C-Type / metabolism
Lung / immunology
Lung / pathology
Lung / virology
Mendelian Randomization Analysis
Nasopharynx / immunology
Nasopharynx / pathology
Nasopharynx / virology
RNA-Seq
Receptors, Cell Surface / genetics*
Receptors, Cell Surface / metabolism
SARS-CoV-2 / immunology*
Severity of Illness Index
Single-Cell Analysis

Substances

CLEC4M protein, human
Cell Adhesion Molecules
DC-specific ICAM-3 grabbing nonintegrin
Lectins, C-Type
Receptors, Cell Surface
ACE2 protein, human
Angiotensin-Converting Enzyme 2