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Smoking and SARS-CoV-2 Impair Dendritic Cells and Regulate DC-SIGN Expression in Tissues
Guoshuai Cai; Yohan Bossé; Mulong Du; Helmut Albrecht; Fei Qin; Xuanxuan Yu; Xizhi Luo; Michelle Androulakis; Xia Zhu; Jun Zhou; Xiang Cui; Changhua Yi; Chao Cheng; Mitz Nagarkatti; Prakash Nagarkatti; David Christiani; Michael Whitfield; Christopher Amos; Feifei Xiao.
Afiliação
  • Guoshuai Cai; University of South Carolina
  • Yohan Bossé; Laval University
  • Mulong Du; Harvard T.H. Chan School of Public Health
  • Helmut Albrecht; Prisma Health Medical Group
  • Fei Qin; Arnold School of Public Health, University of South Carolina
  • Xuanxuan Yu; Arnold School of Public Health, University of South Carolina
  • Xizhi Luo; Arnold School of Public Health, University of South Carolina
  • Michelle Androulakis; Columbia VA Health System
  • Xia Zhu; Arnold School of Public Health, University of South Carolina
  • Jun Zhou; Arnold School of Public Health, University of South Carolina
  • Xiang Cui; Arnold School of Public Health, University of South Carolina
  • Changhua Yi; the Second Hospital of Nanjing, Southeast University
  • Chao Cheng; Baylor College of Medicine
  • Mitz Nagarkatti; School of Medicine, University of South Carolina
  • Prakash Nagarkatti; School of Medicine, University of South Carolina
  • David Christiani; Harvard T.H. Chan School of Public Health
  • Michael Whitfield; Geisel School of Medicine at Dartmouth
  • Christopher Amos; Baylor College of Medicine
  • Feifei Xiao; Arnold School of Public Health, University of South Carolina
Preprint em En | PREPRINT-MEDRXIV | ID: ppmedrxiv-20245316
ABSTRACT
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. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/20245316v1_ufig1.gif" ALT="Figure 1"> View larger version (59K) org.highwire.dtl.DTLVardef@11a509borg.highwire.dtl.DTLVardef@a1faeforg.highwire.dtl.DTLVardef@619bb4org.highwire.dtl.DTLVardef@357bf5_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsSmoking 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.
Licença
cc_by_nc_nd
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-MEDRXIV Tipo de estudo: Observational_studies / Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Preprint
Texto completo: 1 Coleções: 09-preprints Base de dados: PREPRINT-MEDRXIV Tipo de estudo: Observational_studies / Prognostic_studies Idioma: En Ano de publicação: 2020 Tipo de documento: Preprint