Extensive activation, tissue trafficking, turnover and functional impairment of NK cells in COVID-19 patients at disease onset associates with subsequent disease severity.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
07
10
2020
accepted:
03
03
2021
revised:
28
04
2021
pubmed:
17
4
2021
medline:
11
5
2021
entrez:
16
4
2021
Statut:
epublish
Résumé
The SARS-CoV-2 infection causes severe respiratory involvement (COVID-19) in 5-20% of patients through initial immune derangement, followed by intense cytokine production and vascular leakage. Evidence of immune involvement point to the participation of T, B, and NK cells in the lack of control of virus replication leading to COVID-19. NK cells contribute to early phases of virus control and to the regulation of adaptive responses. The precise mechanism of NK cell dysregulation is poorly understood, with little information on tissue margination or turnover. We investigated these aspects by multiparameter flow cytometry in a cohort of 28 patients hospitalized with early COVID-19. Relevant decreases in CD56brightCD16+/- NK subsets were detected, with a shift of circulating NK cells toward more mature CD56dimCD16+KIR+NKG2A+ and "memory" KIR+CD57+CD85j+ cells with increased inhibitory NKG2A and KIR molecules. Impaired cytotoxicity and IFN-γ production were associated with conserved expression of natural cytotoxicity receptors and perforin. Moreover, intense NK cell activation with increased HLA-DR and CD69 expression was associated with the circulation of CD69+CD103+ CXCR6+ tissue-resident NK cells and of CD34+DNAM-1brightCXCR4+ inflammatory precursors to mature functional NK cells. Severe disease trajectories were directly associated with the proportion of CD34+DNAM-1brightCXCR4+ precursors and inversely associated with the proportion of NKG2D+ and of CD103+ NK cells. Intense NK cell activation and trafficking to and from tissues occurs early in COVID-19, and is associated with subsequent disease progression, providing an insight into the mechanism of clinical deterioration. Strategies to positively manipulate tissue-resident NK cell responses may provide advantages to future therapeutic and vaccine approaches.
Identifiants
pubmed: 33861802
doi: 10.1371/journal.ppat.1009448
pii: PPATHOGENS-D-20-02206
pmc: PMC8081333
doi:
Substances chimiques
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009448Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
J Immunol. 2017 Feb 15;198(4):1417-1422
pubmed: 28093522
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Trends Immunol. 2010 Nov;31(11):401-6
pubmed: 20829113
J Exp Med. 2006 Oct 2;203(10):2339-50
pubmed: 17000867
Eur J Immunol. 2004 Aug;34(8):2313-21
pubmed: 15259029
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2886-91
pubmed: 15699323
Nat Commun. 2015 Oct 05;6:8109
pubmed: 26436997
Cytometry A. 2013 Aug;83(8):702-13
pubmed: 23650273
J Exp Med. 1991 Dec 1;174(6):1393-8
pubmed: 1720808
Immun Ageing. 2006 Nov 29;3:10
pubmed: 17134511
Eur J Immunol. 2005 Aug;35(8):2452-8
pubmed: 15997468
Nature. 2020 Mar;579(7798):265-269
pubmed: 32015508
Int Immunol. 2008 Sep;20(9):1155-67
pubmed: 18596023
J Infect Dis. 2020 May 11;221(11):1762-1769
pubmed: 32227123
Clin Microbiol Infect. 2021 Feb;27(2):297-298
pubmed: 32822882
Science. 2011 Jan 7;331(6013):44-9
pubmed: 21212348
J Med Virol. 2020 Nov;92(11):2310-2311
pubmed: 32383174
Nature. 1998 Feb 19;391(6669):795-9
pubmed: 9486650
J Immunol. 2012 Aug 1;189(3):1491-9
pubmed: 22745371
N Engl J Med. 2020 Feb 20;382(8):727-733
pubmed: 31978945
Nat Rev Immunol. 2002 Dec;2(12):957-64
pubmed: 12461568
JAMA. 2020 Mar 17;323(11):1061-1069
pubmed: 32031570
N Engl J Med. 2020 Aug 27;383(9):885-886
pubmed: 32530584
Clin Immunol Immunopathol. 1997 Sep;84(3):269-75
pubmed: 9281385
Clin Infect Dis. 2020 Jul 28;71(15):762-768
pubmed: 32161940
PLoS One. 2020 Aug 20;15(8):e0237831
pubmed: 32817707
J Virol. 2017 Nov 14;91(23):
pubmed: 28956765
Epidemiol Infect. 2009 Dec;137(12):1776-80
pubmed: 19480727
Nature. 2006 Mar 23;440(7083):540-4
pubmed: 16525420
J Allergy Clin Immunol. 2021 Jan 23;:
pubmed: 33493558
J Immunol Methods. 2003 Oct 1;281(1-2):65-78
pubmed: 14580882
Nat Commun. 2019 Aug 26;10(1):3841
pubmed: 31451696
J Transl Med. 2015 Mar 01;13:77
pubmed: 25849716
Gastroenterology. 2010 Apr;138(4):1536-45
pubmed: 20080094
Nat Med. 2020 Oct;26(10):1623-1635
pubmed: 32807934
Blood. 2012 Mar 15;119(11):2665-74
pubmed: 22180440
Trends Microbiol. 2016 Jun;24(6):490-502
pubmed: 27012512
Front Immunol. 2018 Jul 20;9:1671
pubmed: 30079068
Cell Mol Immunol. 2020 May;17(5):533-535
pubmed: 32203188
Nat Med. 2020 Jul;26(7):1070-1076
pubmed: 32514174
Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11970-5
pubmed: 23818644
Eur J Immunol. 2011 Oct;41(10):2905-14
pubmed: 21695691
MMWR Morb Mortal Wkly Rep. 2020 Apr 03;69(13):377-381
pubmed: 32240128
Cell Mol Immunol. 2020 Sep;17(9):995-997
pubmed: 32612152
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Int Immunol. 1998 Jul;10(7):981-9
pubmed: 9701036
Sci Immunol. 2020 Jul 15;5(49):
pubmed: 32669287
J Hepatol. 2011 Aug;55(2):278-88
pubmed: 21168454
Nat Rev Immunol. 2016 Apr 28;16(5):310-20
pubmed: 27121652
Eur J Immunol. 2013 May;43(5):1133-41
pubmed: 23552990
Front Immunol. 2013 Dec 13;4:458
pubmed: 24379818
Eur J Immunol. 2003 Sep;33(9):2410-8
pubmed: 12938217
Exp Gerontol. 1999 Apr;34(2):253-65
pubmed: 10363791