DNA Sensors' Signaling in NK Cells During HHV-6A, HHV-6B and HHV-7 Infection.
DNA sensors
HHV-6A
HHV-6B
HHV-7
human herpesvirus
natural killer cells
Journal
Frontiers in microbiology
ISSN: 1664-302X
Titre abrégé: Front Microbiol
Pays: Switzerland
ID NLM: 101548977
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
07
2019
accepted:
30
01
2020
entrez:
7
3
2020
pubmed:
7
3
2020
medline:
7
3
2020
Statut:
epublish
Résumé
The host DNA sensor proteins TLR9, STING, IFI16 are central signaling molecules that control the innate immune response to cytosolic nucleic acids. Here we propose to investigate how Natural killer (NK) cell infection by human herpesvirus (HHV)-6A, HHV-6B or HHV-7 is able to modify DNA sensor signaling in NK cells. We infected the NK92 cell line and primary NK cells with cell-free inocula of HHV-6A, HHV-6B or HHV-7 and evaluated TLR9, STING, and IFI16 pathway expression by Real-Time PCR, Western Blot, immunofluorescence and flow cytometry for 1, 2, 3, and 6 days post-infection. We evaluated NK cell cytokine-producing by Real-Time PCR and enzyme immunosorbent assay. NK92 and primary NK cells were promptly infected by three viruses, as demonstrated by virus presence (DNA) and transcription (RNA) analysis. Our data show STING/STAT6 up-modulation in HHV-6A infected NK cells. NK cells infected with HHV-6B and HHV-7 up-regulated CCL3, IFN-alpha, TNF-alpha, IL-8 and IFN-gamma and slightly induced IL-4, and CCL4. HHV-6A infected NK cells up-regulated IL-4 and IL-13 and slightly induced IL-10, TNF-alpha, IFN-alpha, and IFN-gamma. For the first time, we demonstrate that HHV-6A, HHV-6B, and HHV-7 infections have a differential impact on intracellular DNA sensors. HHV-6B and HHV-7 mainly lead to the active control of
Identifiants
pubmed: 32140147
doi: 10.3389/fmicb.2020.00226
pmc: PMC7042408
doi:
Types de publication
Journal Article
Langues
eng
Pagination
226Informations de copyright
Copyright © 2020 Bortolotti, Gentili, Caselli, Sicolo, Soffritti, D’Accolti, Barao, Rotola, Di Luca and Rizzo.
Références
Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3516-21
pubmed: 14993594
PLoS Biol. 2011 Mar;9(3):e1000598
pubmed: 21408089
J Infect Dis. 2012 Nov;206(9):1394-8
pubmed: 22962688
Arch Virol. 2014 May;159(5):863-70
pubmed: 24193951
Clin Dev Immunol. 2012;2012:258391
pubmed: 22110530
Cell Mol Immunol. 2017 Jan;14(1):4-13
pubmed: 26972769
Curr Opin Virol. 2011 Dec;1(6):497-512
pubmed: 22180766
Int Immunol. 2006 Jul;18(7):1115-26
pubmed: 16728430
Clin Microbiol Rev. 2005 Jan;18(1):217-45
pubmed: 15653828
PLoS Pathog. 2012 Jan;8(1):e1002498
pubmed: 22291595
J Immunol. 1997 Nov 15;159(10):4966-72
pubmed: 9366423
Eur J Immunol. 2007 Dec;37(12):3424-34
pubmed: 18034422
Cell Host Microbe. 2015 Sep 9;18(3):270-2
pubmed: 26355212
Front Microbiol. 2017 Dec 15;8:2525
pubmed: 29326672
Expert Opin Ther Targets. 2010 Aug;14(8):787-96
pubmed: 20560798
Nat Immunol. 2019 Feb;20(2):152-162
pubmed: 30643259
Viruses. 2017 Dec 01;9(12):
pubmed: 29194419
Nat Commun. 2017 Feb 13;8:14392
pubmed: 28194029
Mol Immunol. 2017 Nov;91:225-237
pubmed: 28968560
J Biol Chem. 2007 May 25;282(21):15319-23
pubmed: 17395581
PLoS Pathog. 2009 Feb;5(2):e1000315
pubmed: 19247444
Nature. 2000 Dec 7;408(6813):740-5
pubmed: 11130078
PLoS Pathog. 2011 Nov;7(11):e1002362
pubmed: 22102813
Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3872-6
pubmed: 7909607
Cell Host Microbe. 2015 Aug 12;18(2):157-68
pubmed: 26235147
Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):E3008-17
pubmed: 23027953
Cell Rep. 2013 May 30;3(5):1355-61
pubmed: 23707065
Viruses. 2019 Mar 12;11(3):
pubmed: 30870969
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13911-6
pubmed: 9811900
Nat Immunol. 2010 May;11(5):373-84
pubmed: 20404851
J Immunol. 2005 Feb 1;174(3):1259-68
pubmed: 15661881
J Virol. 1998 May;72(5):3837-44
pubmed: 9557667
J Alzheimers Dis. 2019;67(4):1379-1389
pubmed: 30689576
J Immunol. 2005 Aug 1;175(3):1619-27
pubmed: 16034101
PLoS Pathog. 2012;8(10):e1002951
pubmed: 23055929
Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11416-21
pubmed: 15272082
PLoS One. 2016 Jul 01;11(7):e0158304
pubmed: 27367597
J Virol. 2016 Oct 14;90(21):9608-9617
pubmed: 27535049
Pediatr Neurol. 2009 Nov;41(5):353-8
pubmed: 19818937
J Immunol. 2005 Aug 1;175(3):1636-42
pubmed: 16034103
J Med Virol. 1995 Mar;45(3):282-3
pubmed: 7775948
J Immunol. 2010 Oct 15;185(8):4681-90
pubmed: 20855881
J Clin Virol. 2006 Dec;37 Suppl 1:S4-10
pubmed: 17276368
Sci Signal. 2012 Mar 06;5(214):ra20
pubmed: 22394562
J Immunol. 2013 Mar 1;190(5):2311-9
pubmed: 23345332
J Immunol. 2003 Oct 1;171(7):3627-35
pubmed: 14500660
J Gen Virol. 1999 Oct;80 ( Pt 10):2705-2712
pubmed: 10573164
J Exp Med. 2003 Aug 4;198(3):513-20
pubmed: 12900525
Front Microbiol. 2017 Oct 31;8:2143
pubmed: 29163428
Mol Cell. 2018 Sep 6;71(5):745-760.e5
pubmed: 30193098
Nature. 2018 Jul;559(7713):269-273
pubmed: 29973723
J Med Virol. 1996 May;49(1):34-40
pubmed: 8732869
Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):E1773-81
pubmed: 25831530
Am J Respir Cell Mol Biol. 2009 Nov;41(5):516-24
pubmed: 19202006
Cancer Res. 2004 Mar 15;64(6):2167-74
pubmed: 15026359
Sci Rep. 2016 Mar 03;6:22579
pubmed: 26934958