Alarmin S100A9 restricts retroviral infection by limiting reverse transcription in human dendritic cells.
Alarmins
/ genetics
Animals
CD4-Positive T-Lymphocytes
/ immunology
Calgranulin B
/ genetics
Cell Line
Cricetulus
HIV-1
/ genetics
Host-Pathogen Interactions
Humans
Langerhans Cells
/ immunology
Leukemia, Experimental
/ prevention & control
Mice
Moloney murine leukemia virus
/ genetics
Retroviridae Infections
/ prevention & control
Reverse Transcription
Transforming Growth Factor beta
/ immunology
Tumor Virus Infections
/ prevention & control
Virus Replication
HIV-1
Langerhans cells
S100A9
innate immunity
viral restriction
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
16 08 2021
16 08 2021
Historique:
revised:
07
05
2021
received:
14
08
2020
accepted:
14
05
2021
pubmed:
15
6
2021
medline:
19
11
2021
entrez:
14
6
2021
Statut:
ppublish
Résumé
Dendritic cells (DC) subsets, like Langerhans cells (LC), are immune cells involved in pathogen sensing. They express specific antimicrobial cellular factors that are able to restrict infection and limit further pathogen transmission. Here, we identify the alarmin S100A9 as a novel intracellular antiretroviral factor expressed in human monocyte-derived and skin-derived LC. The intracellular expression of S100A9 is decreased upon LC maturation and inversely correlates with enhanced susceptibility to HIV-1 infection of LC. Furthermore, silencing of S100A9 in primary human LC relieves HIV-1 restriction while ectopic expression of S100A9 in various cell lines promotes intrinsic resistance to both HIV-1 and MLV infection by acting on reverse transcription. Mechanistically, the intracellular expression of S100A9 alters viral capsid uncoating and reverse transcription. S100A9 also shows potent inhibitory effect against HIV-1 and MMLV reverse transcriptase (RTase) activity in vitro in a divalent cation-dependent manner. Our findings uncover an unexpected intracellular function of the human alarmin S100A9 in regulating antiretroviral immunity in Langerhans cells.
Identifiants
pubmed: 34121210
doi: 10.15252/embj.2020106540
pmc: PMC8365256
doi:
Substances chimiques
Alarmins
0
Calgranulin B
0
S100A9 protein, human
0
Transforming Growth Factor beta
0
Banques de données
GEO
['GSE173939']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e106540Informations de copyright
© 2021 The Authors.
Références
Viruses. 2020 Jun 11;12(6):
pubmed: 32545337
J Gene Med. 2006 Aug;8(8):951-61
pubmed: 16741998
J Clin Invest. 2008 Oct;118(10):3440-52
pubmed: 18776939
J Virol. 2007 Jul;81(13):6858-68
pubmed: 17442711
J Med Chem. 2004 Jan 1;47(1):14-7
pubmed: 14695815
Nature. 2011 May 25;474(7353):654-7
pubmed: 21613998
Front Immunol. 2018 Dec 06;9:2876
pubmed: 30574147
Annu Rev Biochem. 2018 Jun 20;87:621-643
pubmed: 29925260
J Invest Dermatol. 2016 Oct;136(10):1981-1989
pubmed: 27375111
Eur J Immunol. 2001 Feb;31(2):360-8
pubmed: 11180099
J Immunol. 2010 Aug 1;185(3):1633-41
pubmed: 20592277
J Med Chem. 2006 Nov 16;49(23):6646-9
pubmed: 17154493
Cell Mol Immunol. 2020 May;17(5):547-549
pubmed: 31607745
Blood. 2004 Dec 15;104(13):4260-8
pubmed: 15331440
Nat Microbiol. 2019 Nov;4(11):1840-1850
pubmed: 31611641
J Immunol. 2015 Nov 1;195(9):4426-37
pubmed: 26385519
Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9975-80
pubmed: 21628558
Immunol Rev. 2017 Nov;280(1):41-56
pubmed: 29027222
Trends Microbiol. 2017 Mar;25(3):170-172
pubmed: 28190635
Nat Microbiol. 2018 Dec;3(12):1369-1376
pubmed: 30478388
Retrovirology. 2013 Jan 11;10:6
pubmed: 23311681
Immunity. 2010 May 28;32(5):654-69
pubmed: 20451412
Retrovirology. 2013 Oct 24;10:122
pubmed: 24156302
PLoS One. 2009 Sep 21;4(9):e7098
pubmed: 19768115
Cell Host Microbe. 2009 Jul 23;6(1):68-80
pubmed: 19616766
Cell Rep. 2020 Sep 29;32(13):108201
pubmed: 32997983
Front Immunol. 2017 Nov 17;8:1565
pubmed: 29204146
Nat Med. 2001 May;7(5):631-4
pubmed: 11329067
Nature. 2016 Dec 15;540(7633):448-452
pubmed: 27919079
Nat Microbiol. 2020 Sep;5(9):1088-1095
pubmed: 32483230
EMBO J. 2021 Aug 16;40(16):e106540
pubmed: 34121210
Nat Med. 2007 Mar;13(3):367-71
pubmed: 17334373
J Biol Chem. 2015 Jul 31;290(31):18991-8
pubmed: 26055713
J Infect Dis. 1999 May;179 Suppl 3:S413-7
pubmed: 10099109
Antimicrob Agents Chemother. 1994 Dec;38(12):2827-37
pubmed: 7695269
Nat Immunol. 2012 Feb 12;13(3):223-228
pubmed: 22327569
Nat Biotechnol. 2002 Nov;20(11):1151-4
pubmed: 12355096
Methods Mol Biol. 2014;1087:29-36
pubmed: 24158811
Nature. 2011 Nov 06;480(7377):379-82
pubmed: 22056990
Nature. 2011 Jun 29;474(7353):658-61
pubmed: 21720370
Vet Microbiol. 2019 Dec;239:108498
pubmed: 31767072
J Immunol. 2002 Sep 15;169(6):3307-13
pubmed: 12218151
Blood. 2009 May 21;113(21):5157-66
pubmed: 19279330
Cell. 2014 Oct 23;159(3):623-34
pubmed: 25417112
FEMS Immunol Med Microbiol. 2005 Feb 1;43(2):105-14
pubmed: 15681139
J Immunol. 2014 Sep 1;193(5):2554-64
pubmed: 25070850