Natural killer cell immunotypes related to COVID-19 disease severity

Autor: Johan K. Sandberg, Christopher Maucourant, Kristoffer Strålin, Soo Aleman, Iva Filipovic, Jonas Klingström, Marcus Buggert, Olav Rooyackers, Jakob Michaëlsson, Nicole Marquardt, Hans-Gustaf Ljunggren, Björn Reinius, Ryan M. Hull, Niklas K. Björkström, Eivind Heggernes Ask, Demi Brownlie, Martin Cornillet, Antonio Lentini, Angelica Cuapio, Quirin Hammer, Laura Hertwig, Benedikt Strunz, Lars Eriksson, Alvaro Haroun-Izquierdo, Elin Folkesson, Andrea Ponzetta, Karl-Johan Malmberg, Marie Schaffer
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
viruses
Cell
Adaptive Immunity
Lymphocyte Activation
Polymerase Chain Reaction
Severity of Illness Index
SciImmunol r-articles
0302 clinical medicine
Receptors
KIR
Immunopathology
Prospective Studies
Protein Interaction Maps
skin and connective tissue diseases
Receptor
Research Articles
Innate Immune System
biology
medicine.diagnostic_test
General Medicine
Middle Aged
Flow Cytometry
Acquired immune system
CD56 Antigen
Killer Cells
Natural
Phenotype
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
Coronavirus Infections
Research Article
Pneumonia
Viral
Immunology
Infectious Disease
macromolecular substances
Flow cytometry
Natural killer cell
Betacoronavirus
03 medical and health sciences
medicine
Humans
Serologic Tests
Pandemics
Sweden
Innate immune system
SARS-CoV-2
fungi
COVID-19
body regions
Coronavirus
030104 developmental biology
Perforin
biology.protein
Zdroj: Science Immunology
ISSN: 2470-9468
DOI: 10.1126/sciimmunol.abd6832
Popis: The NK cell activation landscape in acute SARS-CoV-2 infection is associated with COVID-19 disease severity.
Activated NK cells in severe COVID-19 Natural killer (NK) cells are cytotoxic lymphocytes that provide innate immune defense against viral infections and cancer, but little is known about their involvement in the host response to COVID-19. Maucourant et al. used high-dimensional flow cytometry to characterize NK cells in patients with moderate or severe COVID-19. SARS-CoV-2 infection was associated with fewer blood NK cells but a higher activation state in circulating NK cells. Severe COVID-19 resulted in an increase in “armed” NK cells containing high levels of cytotoxic proteins such as perforin. The adaptive NK subset was markedly expanded in a subset of severe patients. These findings lay the groundwork for future studies examining the mechanisms of NK cell activation in COVID-19 and their potential roles in host protection and immunopathology.
Understanding innate immune responses in coronavirus disease 2019 (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 single-cell RNA sequencing 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. Last, arming of CD56bright 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.
Databáze: OpenAIRE
Externí odkaz: