High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19.
COVID-19
eosinophil and basophil activation
high-dimensional flow cytometry
neutrophil heterogeneity
viral immune responses
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
05 10 2021
05 10 2021
Historique:
accepted:
21
08
2021
entrez:
22
9
2021
pubmed:
23
9
2021
medline:
2
10
2021
Statut:
ppublish
Résumé
Since the outset of the COVID-19 pandemic, increasing evidence suggests that the innate immune responses play an important role in the disease development. A dysregulated inflammatory state has been proposed as a key driver of clinical complications in COVID-19, with a potential detrimental role of granulocytes. However, a comprehensive phenotypic description of circulating granulocytes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients is lacking. In this study, we used high-dimensional flow cytometry for granulocyte immunophenotyping in peripheral blood collected from COVID-19 patients during acute and convalescent phases. Severe COVID-19 was associated with increased levels of both mature and immature neutrophils, and decreased counts of eosinophils and basophils. Distinct immunotypes were evident in COVID-19 patients, with altered expression of several receptors involved in activation, adhesion, and migration of granulocytes (e.g., CD62L, CD11a/b, CD69, CD63, CXCR4). Paired sampling revealed recovery and phenotypic restoration of the granulocytic signature in the convalescent phase. The identified granulocyte immunotypes correlated with distinct sets of soluble inflammatory markers, supporting pathophysiologic relevance. Furthermore, clinical features, including multiorgan dysfunction and respiratory function, could be predicted using combined laboratory measurements and immunophenotyping. This study provides a comprehensive granulocyte characterization in COVID-19 and reveals specific immunotypes with potential predictive value for key clinical features associated with COVID-19.
Identifiants
pubmed: 34548411
pii: 2109123118
doi: 10.1073/pnas.2109123118
pmc: PMC8501786
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: K.-J.M. is a scientific advisor and has a research grant from Fate Therapeutics and is a member of the Scientific Advisory Board of Vycellix Inc. H.-G.L. is a member of the board of XNK Therapeutics AB and Vycellix Inc. J.-I.H. serves as consultant for Sobi AB.
Références
Nat Commun. 2019 Jul 31;10(1):3422
pubmed: 31366921
Cell. 2020 Oct 1;183(1):158-168.e14
pubmed: 32979941
Trends Immunol. 2019 Jul;40(7):565-583
pubmed: 31160207
J Allergy Clin Immunol. 2020 Jul;146(1):1-7
pubmed: 32344056
Immunity. 2020 Jun 16;52(6):910-941
pubmed: 32505227
Nat Commun. 2018 Sep 24;9(1):3879
pubmed: 30250029
Nat Rev Immunol. 2011 Jul 25;11(8):519-31
pubmed: 21785456
EClinicalMedicine. 2020 May 03;23:100375
pubmed: 32368728
J Clin Invest. 2010 Apr;120(4):1151-64
pubmed: 20237412
Nature. 2020 Aug;584(7821):463-469
pubmed: 32717743
Circulation. 2020 Sep 22;142(12):1176-1189
pubmed: 32755393
Sci Immunol. 2020 Sep 28;5(51):
pubmed: 32989174
JAMA. 2020 Apr 7;323(13):1239-1242
pubmed: 32091533
Am J Respir Cell Mol Biol. 2016 Sep;55(3):387-94
pubmed: 27049514
J Immunol. 2007 Dec 15;179(12):8454-62
pubmed: 18056392
Blood. 2020 Sep 3;136(10):1169-1179
pubmed: 32597954
J Clin Invest. 2016 Sep 1;126(9):3279-95
pubmed: 27548519
Clin Transl Immunology. 2020 Dec 14;9(12):e1224
pubmed: 33343897
Nat Commun. 2020 Oct 16;11(1):5243
pubmed: 33067472
Nat Med. 2020 Jun;26(6):842-844
pubmed: 32398875
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Sci Immunol. 2020 Aug 21;5(50):
pubmed: 32826343
Immunol Res. 2009;43(1-3):128-37
pubmed: 18818885
Front Immunol. 2017 May 12;8:550
pubmed: 28553293
Cell Rep Med. 2020 Aug 25;1(5):100078
pubmed: 32838342
J Allergy Clin Immunol. 2020 Jul;146(1):119-127.e4
pubmed: 32360286
J Allergy Clin Immunol. 2018 Aug;142(2):370-380
pubmed: 29247714
BMC Infect Dis. 2019 Nov 1;19(1):926
pubmed: 31675923
J Immunol. 2017 May 15;198(10):4046-4053
pubmed: 28373583
Nat Rev Immunol. 2013 Jan;13(1):9-22
pubmed: 23154224
Viral Immunol. 2019 Jun;32(5):198-207
pubmed: 31140942
Nat Rev Cancer. 2020 Sep;20(9):485-503
pubmed: 32694624
Clin Mol Allergy. 2016 Nov 1;14:15
pubmed: 27822141
J Virol. 1999 Oct;73(10):8880-3
pubmed: 10482647
J Transl Med. 2020 May 20;18(1):206
pubmed: 32434518
Nat Rev Immunol. 2019 Apr;19(4):255-265
pubmed: 30816340
Travel Med Infect Dis. 2019 May - Jun;29:48-50
pubmed: 30872071
Nat Immunol. 2011 Dec 25;13(2):170-80
pubmed: 22197976
Am J Physiol Lung Cell Mol Physiol. 2017 Nov 1;313(5):L845-L858
pubmed: 28775098
Clin Transl Immunology. 2021 Apr 29;10(4):e1271
pubmed: 33968405
Nat Med. 2020 Oct;26(10):1623-1635
pubmed: 32807934
J Allergy Clin Immunol. 2012 Sep;130(3):572-84
pubmed: 22935586
Immunity. 2020 Aug 18;53(2):303-318.e5
pubmed: 32579887
J Leukoc Biol. 2009 Nov;86(5):1145-51
pubmed: 19638499
Cell Death Differ. 2020 Nov;27(11):3196-3207
pubmed: 32514047
Nat Med. 2020 Jul;26(7):1070-1076
pubmed: 32514174
Cell. 2020 Sep 17;182(6):1419-1440.e23
pubmed: 32810438
Cell. 2020 Sep 17;182(6):1401-1418.e18
pubmed: 32810439
Nat Immunol. 2020 Sep;21(9):1119-1133
pubmed: 32719519
Nat Biotechnol. 2020 Aug;38(8):970-979
pubmed: 32591762
Cell. 2020 May 28;181(5):1036-1045.e9
pubmed: 32416070
EBioMedicine. 2020 May;55:102763
pubmed: 32361250
Lancet. 2020 Mar 28;395(10229):1033-1034
pubmed: 32192578
Nat Rev Immunol. 2014 May;14(5):302-14
pubmed: 24751955
EBioMedicine. 2020 Aug;58:102925
pubmed: 32745993
Immunology. 2021 Jan;162(1):92-104
pubmed: 32955733
Nat Protoc. 2020 Apr;15(4):1484-1506
pubmed: 32103204
J Exp Med. 2020 Jun 1;217(6):
pubmed: 32302401
Proc Natl Acad Sci U S A. 2019 Dec 10;116(50):25222-25228
pubmed: 31754025
PLoS Pathog. 2014 Mar 13;10(3):e1003993
pubmed: 24626392
Science. 2020 Aug 7;369(6504):718-724
pubmed: 32661059
J Virol. 2015 Aug;89(15):8050-62
pubmed: 26018157