Natural killer cell immunotypes related to COVID-19 disease severity

Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color fl...

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Veröffentlicht in:Science immunology Jg. 5; H. 50
Hauptverfasser: Maucourant, Christopher, Filipovic, Iva, Ponzetta, Andrea, Aleman, Soo, Cornillet, Martin, Hertwig, Laura, Strunz, Benedikt, Lentini, Antonio, Reinius, Björn, Brownlie, Demi, Cuapio, Angelica, Ask, Eivind Heggernes, Hull, Ryan M, Haroun-Izquierdo, Alvaro, Schaffer, Marie, Klingström, Jonas, Folkesson, Elin, Buggert, Marcus, Sandberg, Johan K, Eriksson, Lars I, Rooyackers, Olav, Ljunggren, Hans-Gustaf, Malmberg, Karl-Johan, Michaëlsson, Jakob, Marquardt, Nicole, Hammer, Quirin, Strålin, Kristoffer, Björkström, Niklas K
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 21.08.2020
Schlagworte:
Adaptive Immunity
Betacoronavirus - genetics
Betacoronavirus - immunology
CD56 Antigen - metabolism
Coronavirus Infections - blood
Coronavirus Infections - epidemiology
Coronavirus Infections - immunology
Coronavirus Infections - pathology
COVID-19
Female
Flow Cytometry - methods
Humans
Killer Cells, Natural - immunology
Lymphocyte Activation
Male
Middle Aged
Pandemics
Phenotype
Pneumonia, Viral - blood
Pneumonia, Viral - epidemiology
Pneumonia, Viral - immunology
Pneumonia, Viral - pathology
Polymerase Chain Reaction
Prospective Studies
Protein Interaction Maps - immunology
Receptors, KIR - metabolism
SARS-CoV-2
Serologic Tests
Severity of Illness Index
Sweden - epidemiology
Sweden
ISSN:2470-9468, 2470-9468
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Zusammenfassung:Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients. This pattern was mirrored in scRNA-seq signatures of NK cells in bronchoalveolar lavage from COVID-19 patients. Unsupervised high-dimensional analysis of peripheral blood NK cells furthermore identified distinct NK cell immunotypes that were linked to disease severity. Hallmarks of these immunotypes were high expression of perforin, NKG2C, and Ksp37, reflecting increased presence of adaptive NK cells in circulation of patients with severe disease. Finally, arming of CD56 NK cells was observed across COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This study provides a detailed map of the NK cell activation landscape in COVID-19 disease.
Bibliographie:ObjectType-Article-1
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content type line 23
ISSN:2470-9468
2470-9468
DOI:10.1126/sciimmunol.abd6832