期刊
SCIENCE IMMUNOLOGY
卷 5, 期 50, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abd6832
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资金
- Swedish Research Council
- Swedish Cancer Society
- Swedish Foundation for Strategic Research
- Knut and Alice Wallenberg Foundation
- Nordstjernan AB
- Center for Innovative Medicine at Karolinska Institutet
- Region Stockholm
- SRP Diabetes Karolinska Institutet
- StratRegen Karolinska Institutet
- Karolinska Institutet
- Wenner-Gren Foundations
- European Molecular Biology Organization [EMBO ALTF 802-2018]
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 CD56(bright) 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.
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