Natural killer cell immunotypes related to COVID-19 disease severity.
Christopher MaucourantIva FilipovicAndrea PonzettaSoo AlemanMartin Cornillet JeanninLaura HertwigBenedikt StrunzAntonio LentiniBjörn ReiniusDemi BrownlieAngelica CuapioEivind Heggernes AskRyan M HullAlvaro Haroun-IzquierdoMarie SchafferJonas KlingströmElin FolkessonMarcus BuggertJohan K SandbergLars I ErikssonOlav RooyackersHans-Gustaf LjunggrenKarl-Johan MalmbergJakob MichaëlssonNicole MarquardtQuirin HammerKristoffer StrålinNiklas K Björkströmnull nullPublished in: Science immunology (2020)
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 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.
Keyphrases
- nk cells
- sars cov
- peripheral blood
- coronavirus disease
- immune response
- single cell
- flow cytometry
- protein protein
- respiratory syndrome coronavirus
- genome wide
- small molecule
- oxidative stress
- machine learning
- stem cells
- hepatitis b virus
- toll like receptor
- drug induced
- mesenchymal stem cells
- dna methylation
- intensive care unit
- cell therapy
- respiratory failure
- rna seq
- long non coding rna
- aortic dissection
- network analysis