Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19
Standard
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19. / Krämer, Benjamin; Knoll, Rainer; Bonaguro, Lorenzo; ToVinh, Michael; Raabe, Jan; Astaburuaga-García, Rosario; Schulte-Schrepping, Jonas; Kaiser, Kim Melanie; Rieke, Gereon J; Bischoff, Jenny; Monin, Malte B; Hoffmeister, Christoph; Schlabe, Stefan; De Domenico, Elena; Reusch, Nico; Händler, Kristian; Reynolds, Gary; Blüthgen, Nils; Hack, Gudrun; Finnemann, Claudia; Nischalke, Hans D; Strassburg, Christian P; Stephenson, Emily; Su, Yapeng; Gardner, Louis; Yuan, Dan; Chen, Daniel; Goldman, Jason; Rosenstiel, Philipp; Schmidt, Susanne V; Latz, Eicke; Hrusovsky, Kevin; Ball, Andrew J; Johnson, Joe M; Koenig, Paul-Albert; Schmidt, Florian I; Haniffa, Muzlifah; Heath, James R; Kümmerer, Beate M; Keitel, Verena; Jensen, Björn; Stubbemann, Paula; Kurth, Florian; Sander, Leif E; Sawitzki, Birgit; Aschenbrenner, Anna C; Schultze, Joachim L; Nattermann, Jacob; Deutsche COVID-19 OMICS Initiative (DeCOI).
In: IMMUNITY, Vol. 54, No. 11, 09.11.2021, p. 2650-2669.e14.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19
AU - Krämer, Benjamin
AU - Knoll, Rainer
AU - Bonaguro, Lorenzo
AU - ToVinh, Michael
AU - Raabe, Jan
AU - Astaburuaga-García, Rosario
AU - Schulte-Schrepping, Jonas
AU - Kaiser, Kim Melanie
AU - Rieke, Gereon J
AU - Bischoff, Jenny
AU - Monin, Malte B
AU - Hoffmeister, Christoph
AU - Schlabe, Stefan
AU - De Domenico, Elena
AU - Reusch, Nico
AU - Händler, Kristian
AU - Reynolds, Gary
AU - Blüthgen, Nils
AU - Hack, Gudrun
AU - Finnemann, Claudia
AU - Nischalke, Hans D
AU - Strassburg, Christian P
AU - Stephenson, Emily
AU - Su, Yapeng
AU - Gardner, Louis
AU - Yuan, Dan
AU - Chen, Daniel
AU - Goldman, Jason
AU - Rosenstiel, Philipp
AU - Schmidt, Susanne V
AU - Latz, Eicke
AU - Hrusovsky, Kevin
AU - Ball, Andrew J
AU - Johnson, Joe M
AU - Koenig, Paul-Albert
AU - Schmidt, Florian I
AU - Haniffa, Muzlifah
AU - Heath, James R
AU - Kümmerer, Beate M
AU - Keitel, Verena
AU - Jensen, Björn
AU - Stubbemann, Paula
AU - Kurth, Florian
AU - Sander, Leif E
AU - Sawitzki, Birgit
AU - Aschenbrenner, Anna C
AU - Schultze, Joachim L
AU - Nattermann, Jacob
AU - Deutsche COVID-19 OMICS Initiative (DeCOI)
N1 - Copyright © 2021 Elsevier Inc. All rights reserved.
PY - 2021/11/9
Y1 - 2021/11/9
N2 - 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.
AB - 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.
KW - Base Sequence
KW - COVID-19/immunology
KW - Humans
KW - Immunity, Innate/immunology
KW - Inflammation/immunology
KW - Interferon-alpha/blood
KW - Killer Cells, Natural/immunology
KW - Pulmonary Fibrosis/pathology
KW - RNA-Seq
KW - SARS-CoV-2/immunology
KW - Severity of Illness Index
KW - Transcriptome/genetics
KW - Tumor Necrosis Factor-alpha/metabolism
KW - United Kingdom
KW - United States
U2 - 10.1016/j.immuni.2021.09.002
DO - 10.1016/j.immuni.2021.09.002
M3 - SCORING: Journal article
C2 - 34592166
VL - 54
SP - 2650-2669.e14
JO - IMMUNITY
JF - IMMUNITY
SN - 1074-7613
IS - 11
ER -