Details

Autor(en) / Beteiligte

• Krämer, Benjamin
• Bonaguro, Lorenzo
• ToVinh, Michael
• Astaburuaga-García, Rosario
• Schulte-Schrepping, Jonas
• Kaiser, Kim Melanie
• Rieke, Gereon J.
• Monin, Malte B.
• Hoffmeister, Christoph
• Schlabe, Stefan
• De Domenico, Elena
• Reusch, Nico
• Händler, Kristian
• Reynolds, Gary
• Hack, Gudrun
• Finnemann, Claudia
• Strassburg, Christian P.
• Stephenson, Emily
• Su, Yapeng
• Gardner, Louis
• Yuan, Dan
• Goldman, Jason
• Hrusovsky, Kevin
• Ball, Andrew J.
• Johnson, Joe M.
• Koenig, Paul-Albert
• Schmidt, Florian I.
• Haniffa, Muzlifah
• Kümmerer, Beate M.
• Keitel, Verena
• Jensen, Björn
• Sander, Leif E.
• Aschenbrenner, Anna C.
• Bals, Robert
• Becker, Matthias
• Bezdan, Daniela
• Bitzer, Michael
• Bork, Peer
• Boyke, Bunk
• Blum, Helmut
• Colome-Tatche, Maria
• Diefenbach, Andreas
• Dilthey, Alexander
• Franzenburg, Sören
• Frick, Julia-Stefanie
• Ganzenmueller, Tina
• Gauder, Marie
• Grundhoff, Adam
• Grundmann, Hajo
• Hanses, Frank
• Hehr, Ute
• Heimbach, André
• Horn, Friedemann
• Iftner, Angelika
• Illig, Thomas
• Janssen, Stefan
• Kalinowski, Jörn
• Keller, Andreas
• Kim-Hellmuth, Sarah
• Klein, Christoph
• Knop, Michael
• Kohlbacher, Oliver
• Köhrer, Karl
• Kühnert, Denise
• Kurth, Ingo
• Landthaler, Markus
• Li, Yang
• Makarewicz, Oliwia
• McHardy, Alice C.
• Mertes, Christian
• Münchhoff, Maximilian
• Nahnsen, Sven
• Ntoumi, Francine
• Ossowski, Stephan
• Overmann, Jörg
• Peter, Silke
• Pfeffer, Klaus
• Pink, Isabell
• Poetsch, Anna R.
• Protzer, Ulrike
• Rajewsky, Nikolaus
• Ripke, Stephan
• Nunes da Rocha, Ulisses
• Rosenstiel, Philip
• Sander, Leif Erik
• Sawitzki, Birgit
• Schiffer, Philipp
• Schmid-Burgk, Jonathan
• Schultze, Joachim L.
• Sczyrba, Alexander
• Sharaf, Mariam L.
• Singh, Yogesh
• Stegle, Oliver
• Ulas, Thomas
• Velavan, Thirumalaisamy P.
• Vogel, Jörg
• Wieczorek, Dagmar
• Winkler, Sylke

Titel

Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19

Ist Teil von

• Immunity (Cambridge, Mass.), 2021-11, Vol.54 (11), p.2650-2669.e14

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •Elevated IFN-α plasma levels characteristic for early severe COVID-19 (sCOVID-19)•Differential IFN-α vs. TNF signaling discriminates severe vs. moderate COVID-19•NK cells exert anti-SARS-CoV-2 activity but are functionally impaired in sCOVID-19•Persistent NK cell dysfunction may promote fibrotic lung disease in sCOVID-19 The importance of NK cells in the innate response to viral infection provides rationale for deeper understanding of their role in COVID-19. Here, Krämer et al. utilize longitudinal analysis of NK cells to show early TNF and IFN-α signatures associated with moderate and severe COVID-19, respectively, and NK cell functional impairment in severe disease.