tetano
Editor, Senior Moderator
Immunity
. 2021 Sep 4;S1074-7613(21)00365-4.
doi: 10.1016/j.immuni.2021.09.002. Online ahead of print.
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19
Benjamin Krämer[SUP] 1 [/SUP], Rainer Knoll[SUP] 2 [/SUP], Lorenzo Bonaguro[SUP] 2 [/SUP], Michael ToVinh[SUP] 1 [/SUP], Jan Raabe[SUP] 1 [/SUP], Rosario Astaburuaga-García[SUP] 3 [/SUP], Jonas Schulte-Schrepping[SUP] 2 [/SUP], Kim Melanie Kaiser[SUP] 1 [/SUP], Gereon J Rieke[SUP] 1 [/SUP], Jenny Bischoff[SUP] 1 [/SUP], Malte B Monin[SUP] 1 [/SUP], Christoph Hoffmeister[SUP] 1 [/SUP], Stefan Schlabe[SUP] 4 [/SUP], Elena De Domenico[SUP] 5 [/SUP], Nico Reusch[SUP] 2 [/SUP], Kristian Händler[SUP] 5 [/SUP], Gary Reynolds[SUP] 6 [/SUP], Nils Blüthgen[SUP] 3 [/SUP], Gudrun Hack[SUP] 1 [/SUP], Claudia Finnemann[SUP] 1 [/SUP], Hans D Nischalke[SUP] 1 [/SUP], Christian P Strassburg[SUP] 1 [/SUP], Emily Stephenson[SUP] 6 [/SUP], Yapeng Su[SUP] 7 [/SUP], Louis Gardner[SUP] 6 [/SUP], Dan Yuan[SUP] 7 [/SUP], Daniel Chen[SUP] 7 [/SUP], Jason Goldman[SUP] 8 [/SUP], Philipp Rosenstiel[SUP] 9 [/SUP], Susanne V Schmidt[SUP] 10 [/SUP], Eicke Latz[SUP] 10 [/SUP], Kevin Hrusovsky[SUP] 11 [/SUP], Andrew J Ball[SUP] 11 [/SUP], Joe M Johnson[SUP] 11 [/SUP], Paul-Albert Koenig[SUP] 12 [/SUP], Florian I Schmidt[SUP] 12 [/SUP], Muzlifah Haniffa[SUP] 13 [/SUP], James R Heath[SUP] 14 [/SUP], Beate M Kümmerer[SUP] 15 [/SUP], Verena Keitel[SUP] 16 [/SUP], Björn Jensen[SUP] 16 [/SUP], Paula Stubbemann[SUP] 17 [/SUP], Florian Kurth[SUP] 18 [/SUP], Leif E Sander[SUP] 18 [/SUP], Birgit Sawitzki[SUP] 19 [/SUP], Deutsche COVID-19 OMICS Initiative (DeCOI); Anna C Aschenbrenner[SUP] 21 [/SUP], Joachim L Schultze[SUP] 22 [/SUP], Jacob Nattermann[SUP] 23 [/SUP]
Collaborators, Affiliations
Abstract
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.
Keywords: COVID-19; NK cells; TNF; antiviral; lung fibrosis; moderate; proteomics; scRNA-seq; severe; type 1 IFN.
. 2021 Sep 4;S1074-7613(21)00365-4.
doi: 10.1016/j.immuni.2021.09.002. Online ahead of print.
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19
Benjamin Krämer[SUP] 1 [/SUP], Rainer Knoll[SUP] 2 [/SUP], Lorenzo Bonaguro[SUP] 2 [/SUP], Michael ToVinh[SUP] 1 [/SUP], Jan Raabe[SUP] 1 [/SUP], Rosario Astaburuaga-García[SUP] 3 [/SUP], Jonas Schulte-Schrepping[SUP] 2 [/SUP], Kim Melanie Kaiser[SUP] 1 [/SUP], Gereon J Rieke[SUP] 1 [/SUP], Jenny Bischoff[SUP] 1 [/SUP], Malte B Monin[SUP] 1 [/SUP], Christoph Hoffmeister[SUP] 1 [/SUP], Stefan Schlabe[SUP] 4 [/SUP], Elena De Domenico[SUP] 5 [/SUP], Nico Reusch[SUP] 2 [/SUP], Kristian Händler[SUP] 5 [/SUP], Gary Reynolds[SUP] 6 [/SUP], Nils Blüthgen[SUP] 3 [/SUP], Gudrun Hack[SUP] 1 [/SUP], Claudia Finnemann[SUP] 1 [/SUP], Hans D Nischalke[SUP] 1 [/SUP], Christian P Strassburg[SUP] 1 [/SUP], Emily Stephenson[SUP] 6 [/SUP], Yapeng Su[SUP] 7 [/SUP], Louis Gardner[SUP] 6 [/SUP], Dan Yuan[SUP] 7 [/SUP], Daniel Chen[SUP] 7 [/SUP], Jason Goldman[SUP] 8 [/SUP], Philipp Rosenstiel[SUP] 9 [/SUP], Susanne V Schmidt[SUP] 10 [/SUP], Eicke Latz[SUP] 10 [/SUP], Kevin Hrusovsky[SUP] 11 [/SUP], Andrew J Ball[SUP] 11 [/SUP], Joe M Johnson[SUP] 11 [/SUP], Paul-Albert Koenig[SUP] 12 [/SUP], Florian I Schmidt[SUP] 12 [/SUP], Muzlifah Haniffa[SUP] 13 [/SUP], James R Heath[SUP] 14 [/SUP], Beate M Kümmerer[SUP] 15 [/SUP], Verena Keitel[SUP] 16 [/SUP], Björn Jensen[SUP] 16 [/SUP], Paula Stubbemann[SUP] 17 [/SUP], Florian Kurth[SUP] 18 [/SUP], Leif E Sander[SUP] 18 [/SUP], Birgit Sawitzki[SUP] 19 [/SUP], Deutsche COVID-19 OMICS Initiative (DeCOI); Anna C Aschenbrenner[SUP] 21 [/SUP], Joachim L Schultze[SUP] 22 [/SUP], Jacob Nattermann[SUP] 23 [/SUP]
Collaborators, Affiliations
- PMID: 34592166
- DOI: 10.1016/j.immuni.2021.09.002
Abstract
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.
Keywords: COVID-19; NK cells; TNF; antiviral; lung fibrosis; moderate; proteomics; scRNA-seq; severe; type 1 IFN.