SARS-CoV-2 suppresses TLR4-induced immunity by dendritic cells via C-type lectin receptor DC-SIGN.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
14
07
2023
accepted:
02
10
2023
revised:
26
10
2023
medline:
30
10
2023
pubmed:
16
10
2023
entrez:
16
10
2023
Statut:
epublish
Résumé
SARS-CoV-2 causes COVID-19, an infectious disease with symptoms ranging from a mild cold to severe pneumonia, inflammation, and even death. Although strong inflammatory responses are a major factor in causing morbidity and mortality, superinfections with bacteria during severe COVID-19 often cause pneumonia, bacteremia and sepsis. Aberrant immune responses might underlie increased sensitivity to bacteria during COVID-19 but the mechanisms remain unclear. Here we investigated whether SARS-CoV-2 directly suppresses immune responses to bacteria. We studied the functionality of human dendritic cells (DCs) towards a variety of bacterial triggers after exposure to SARS-CoV-2 Spike (S) protein and SARS-CoV-2 primary isolate (hCoV-19/Italy). Notably, pre-exposure of DCs to either SARS-CoV-2 S protein or a SARS-CoV-2 isolate led to reduced type I interferon (IFN) and cytokine responses in response to Toll-like receptor (TLR)4 agonist lipopolysaccharide (LPS), whereas other TLR agonists were not affected. SARS-CoV-2 S protein interacted with the C-type lectin receptor DC-SIGN and, notably, blocking DC-SIGN with antibodies restored type I IFN and cytokine responses to LPS. Moreover, blocking the kinase Raf-1 by a small molecule inhibitor restored immune responses to LPS. These results suggest that SARS-CoV-2 modulates DC function upon TLR4 triggering via DC-SIGN-induced Raf-1 pathway. These data imply that SARS-CoV-2 actively suppresses DC function via DC-SIGN, which might account for the higher mortality rates observed in patients with COVID-19 and bacterial superinfections.
Identifiants
pubmed: 37844099
doi: 10.1371/journal.ppat.1011735
pii: PPATHOGENS-D-23-01162
pmc: PMC10602378
doi:
Substances chimiques
DC-specific ICAM-3 grabbing nonintegrin
0
spike protein, SARS-CoV-2
0
Toll-Like Receptor 4
0
Lipopolysaccharides
0
Lectins, C-Type
0
Cytokines
0
TLR4 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1011735Informations de copyright
Copyright: © 2023 van der Donk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Cell Host Microbe. 2014 Jul 9;16(1):31-42
pubmed: 25011106
Nat Rev Immunol. 2001 Nov;1(2):135-45
pubmed: 11905821
Virulence. 2013 Aug 15;4(6):433-4
pubmed: 23863600
ACS Cent Sci. 2021 Jul 28;7(7):1156-1165
pubmed: 34341769
Clin Microbiol Infect. 2020 Dec;26(12):1622-1629
pubmed: 32711058
Methods Mol Biol. 2016;1390:121-9
pubmed: 26803626
Signal Transduct Target Ther. 2021 Aug 4;6(1):291
pubmed: 34344870
Immunity. 2020 Oct 13;53(4):864-877.e5
pubmed: 32791036
Immunity. 2007 May;26(5):605-16
pubmed: 17462920
Nature. 2020 Dec;588(7838):498-502
pubmed: 32805734
JAMA. 2020 Aug 25;324(8):782-793
pubmed: 32648899
Cell Host Microbe. 2016 Jun 8;19(6):760-9
pubmed: 27281568
EMBO J. 2021 Oct 18;40(20):e106765
pubmed: 34510494
Exp Mol Med. 2021 Nov;53(11):1647-1668
pubmed: 34782737
Cell. 2000 Mar 3;100(5):575-85
pubmed: 10721994
JAMA. 2020 Mar 17;323(11):1061-1069
pubmed: 32031570
Eur J Immunol. 2022 Apr;52(4):646-655
pubmed: 35099061
Cell Mol Life Sci. 2021 Feb;78(4):1423-1444
pubmed: 33084946
J Infect Dis. 2010 Apr 15;201(8):1273-4; author reply 1274-5
pubmed: 20225961
J Biol Chem. 1999 Apr 16;274(16):10689-92
pubmed: 10196138
Cell Res. 2021 Jul;31(7):818-820
pubmed: 33742149
Mediators Inflamm. 2021 Jan 14;2021:8874339
pubmed: 33505220
J Exp Med. 2003 Jan 6;197(1):7-17
pubmed: 12515809
Nat Rev Immunol. 2009 Jul;9(7):465-79
pubmed: 19521399
Am J Respir Crit Care Med. 2021 Oct 15;204(8):921-932
pubmed: 34409924
Nat Commun. 2014 May 28;5:3898
pubmed: 24867235
Nat Commun. 2017 Mar 28;8:14954
pubmed: 28348411
Annu Rev Immunol. 2002;20:197-216
pubmed: 11861602
Trends Immunol. 2020 Dec;41(12):1100-1115
pubmed: 33132005
Chest. 2022 Apr;161(4):989-998
pubmed: 34655568
J Mol Cell Biol. 2021 Mar 10;12(12):916-932
pubmed: 33295606
Nat Rev Microbiol. 2011 Apr;9(4):291-306
pubmed: 21383764
Nat Microbiol. 2020 Apr;5(4):562-569
pubmed: 32094589
Clin Microbiol Infect. 2021 Jan;27(1):83-88
pubmed: 32745596
J Med Virol. 2020 Oct;92(10):2105-2113
pubmed: 32383269
Nat Immunol. 2017 Feb;18(2):225-235
pubmed: 28024153
Clin Infect Dis. 2020 Dec 3;71(9):2459-2468
pubmed: 32358954
J Med Virol. 2020 Oct;92(10):1699-1700
pubmed: 32352574
Nat Immunol. 2009 Oct;10(10):1081-8
pubmed: 19718030
Pneumonia (Nathan). 2021 Apr 25;13(1):5
pubmed: 33894790
Science. 2020 Jul 17;369(6501):330-333
pubmed: 32366695
Signal Transduct Target Ther. 2021 Nov 15;6(1):396
pubmed: 34782609
Expert Rev Anti Infect Ther. 2012 Mar;10(3):369-80
pubmed: 22397569
PLoS Pathog. 2021 Oct 6;17(10):e1009742
pubmed: 34614036
Lancet. 2020 Feb 15;395(10223):507-513
pubmed: 32007143
Mol Cell. 2014 Apr 24;54(2):321-8
pubmed: 24766896
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
PLoS Pathog. 2021 May 20;17(5):e1009576
pubmed: 34015061
Crit Care. 2021 Apr 21;25(1):153
pubmed: 33882991
Nat Rev Immunol. 2003 Sep;3(9):697-709
pubmed: 12949494
PLoS One. 2021 May 6;16(5):e0251170
pubmed: 33956882
PLoS One. 2021 Jul 13;16(7):e0254671
pubmed: 34255801
Heliyon. 2021 Feb 02;7(2):e06187
pubmed: 33644468
Clin Chem. 2020 Apr 1;66(4):549-555
pubmed: 32031583
Pathogens. 2022 Apr 07;11(4):
pubmed: 35456120