Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.
Base Sequence
COVID-19
/ immunology
Humans
Immunity, Innate
/ immunology
Inflammation
/ immunology
Interferon-alpha
/ blood
Killer Cells, Natural
/ immunology
Pulmonary Fibrosis
/ pathology
RNA-Seq
SARS-CoV-2
/ immunology
Severity of Illness Index
Transcriptome
/ genetics
Tumor Necrosis Factor-alpha
/ metabolism
United Kingdom
United States
COVID-19
NK cells
TNF
antiviral
lung fibrosis
moderate
proteomics
scRNA-seq
severe
type 1 IFN
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
09 11 2021
09 11 2021
Historique:
received:
19
02
2021
revised:
04
06
2021
accepted:
31
08
2021
pubmed:
1
10
2021
medline:
24
11
2021
entrez:
30
9
2021
Statut:
ppublish
Résumé
Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.
Identifiants
pubmed: 34592166
pii: S1074-7613(21)00365-4
doi: 10.1016/j.immuni.2021.09.002
pmc: PMC8416549
pii:
doi:
Substances chimiques
IFNA1 protein, human
0
Interferon-alpha
0
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2650-2669.e14Investigateurs
Janine Altmüller
(J)
Angel Angelov
(A)
Anna C Aschenbrenner
(AC)
Robert Bals
(R)
Alexander Bartholomäus
(A)
Anke Becker
(A)
Matthias Becker
(M)
Daniela Bezdan
(D)
Michael Bitzer
(M)
Conny Blumert
(C)
Ezio Bonifacio
(E)
Peer Bork
(P)
Bunk Boyke
(B)
Helmut Blum
(H)
Nicolas Casadei
(N)
Thomas Clavel
(T)
Maria Colome-Tatche
(M)
Markus Cornberg
(M)
Inti Alberto De La Rosa Velázquez
(IA)
Andreas Diefenbach
(A)
Alexander Dilthey
(A)
Nicole Fischer
(N)
Konrad Förstner
(K)
Sören Franzenburg
(S)
Julia-Stefanie Frick
(JS)
Gisela Gabernet
(G)
Julien Gagneur
(J)
Tina Ganzenmueller
(T)
Marie Gauder
(M)
Janina Geißert
(J)
Alexander Goesmann
(A)
Siri Göpel
(S)
Adam Grundhoff
(A)
Hajo Grundmann
(H)
Torsten Hain
(T)
Frank Hanses
(F)
Ute Hehr
(U)
André Heimbach
(A)
Marius Hoeper
(M)
Friedemann Horn
(F)
Daniel Hübschmann
(D)
Michael Hummel
(M)
Thomas Iftner
(T)
Angelika Iftner
(A)
Thomas Illig
(T)
Stefan Janssen
(S)
Jörn Kalinowski
(J)
René Kallies
(R)
Birte Kehr
(B)
Andreas Keller
(A)
Oliver T Keppler
(OT)
Sarah Kim-Hellmuth
(S)
Christoph Klein
(C)
Michael Knop
(M)
Oliver Kohlbacher
(O)
Karl Köhrer
(K)
Jan Korbel
(J)
Peter G Kremsner
(PG)
Denise Kühnert
(D)
Ingo Kurth
(I)
Markus Landthaler
(M)
Yang Li
(Y)
Kerstin U Ludwig
(KU)
Oliwia Makarewicz
(O)
Federico Marini
(F)
Manja Marz
(M)
Alice C McHardy
(AC)
Christian Mertes
(C)
Maximilian Münchhoff
(M)
Sven Nahnsen
(S)
Markus Nöthen
(M)
Francine Ntoumi
(F)
Peter Nürnberg
(P)
Stephan Ossowski
(S)
Jörg Overmann
(J)
Silke Peter
(S)
Klaus Pfeffer
(K)
Isabell Pink
(I)
Anna R Poetsch
(AR)
Ulrike Protzer
(U)
Alfred Pühler
(A)
Nikolaus Rajewsky
(N)
Markus Ralser
(M)
Kristin Reiche
(K)
Olaf Rieß
(O)
Stephan Ripke
(S)
Ulisses Nunes da Rocha
(U)
Philip Rosenstiel
(P)
Antoine-Emmanuel Saliba
(AE)
Leif Erik Sander
(LE)
Birgit Sawitzki
(B)
Simone Scheithauer
(S)
Philipp Schiffer
(P)
Jonathan Schmid-Burgk
(J)
Wulf Schneider
(W)
Eva-Christina Schulte
(EC)
Joachim L Schultze
(JL)
Alexander Sczyrba
(A)
Mariam L Sharaf
(ML)
Yogesh Singh
(Y)
Michael Sonnabend
(M)
Oliver Stegle
(O)
Jens Stoye
(J)
Fabian Theis
(F)
Thomas Ulas
(T)
Janne Vehreschild
(J)
Thirumalaisamy P Velavan
(TP)
Jörg Vogel
(J)
Sonja Volland
(S)
Max von Kleist
(M)
Andreas Walker
(A)
Jörn Walter
(J)
Dagmar Wieczorek
(D)
Sylke Winkler
(S)
John Ziebuhr
(J)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests P.-A.K. and F.I.S. are cofounders and shareholders of Dioscure Therapeutics SE. F.I.S. is a consultant and shareholder of IFM Therapeutics. J.R.H. is founder and board member of Isoplexis and PACT Pharma. J.D.G. declares contracted research with Gilead, Lilly, and Regeneron. K.H., J.M.J., and A.J.B. work at Quanterix Corporation. All other authors declare no competing interests.
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