Journal
NATURE
Volume 600, Issue 7888, Pages 295-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-04142-6
Keywords
-
Categories
Funding
- DFG [INST 335/597-1 FUGG, INST 335/777-1 FUGG]
- Deutsche Forschungsgemeinschaft [TR-SFB 84/A02, TR-SFB 84/A06, TR-SFB241/A01, SPP1937-DI764/7, TRR130/P16, TRR130/P17, TR-SFB 84/A07, TRR241/A04, RA 2491/1-1, SFB-TR 84/B08, SFB 1449/Z02]
- European Research Council [ERC-2010-AdG 268978]
- Einstein Foundation Berlin (Einstein Professorship)
- state of Berlin
- European Regional Development Fund (ERDF 2014-2020, Deutsches Rheuma-Forschungszentrum) [EFRE 1.8/11]
- Berlin Institute of Health
- Russian Ministry of Science and Higher Education of the Russian Federation [075-152019-1660]
- Russian Foundation for Basic Research [17-00-00268]
- Leibniz Association (Leibniz Collaborative Excellence, TargArt)
- German Federal Ministry of Education and Research (BMBF) [FKZ: 01KX2021, AP-4, 01KI20337, 82DZL009B1]
- Fondazione AIRC per la Ricerca sul Cancro
- NIAID-NIH CEIRS [HHSN272201400008C]
- Rahel Hirsch Habilitationsstipendium
- BMBF (Organostrat, Defeat Pandemics)
Ask authors/readers for more resources
Research shows that the status of NK cells in COVID-19 patients is negatively correlated with viral load, and NK cells can control SARS-CoV-2 replication by recognizing infected target cells. In severe COVID-19 patients, NK cells exhibit defects in virus control, cytokine production, and cell-mediated cytotoxicity despite high expression of cytotoxic effector molecules.
SARS-CoV-2 is a single-stranded RNA virus that causes COVID-19. Given its acute and often self-limiting course, it is likely that components of the innate immune system play a central part in controlling virus replication and determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a broad range of viruses, including RNA viruses(1,2). NK cell function may be altered during COVID-19 despite increased representation of NK cells with an activated and adaptive phenotype(3,4). Here we show that a decline in viral load in COVID-19 correlates with NK cell status and that NK cells can control SARS-CoV-2 replication by recognizing infected target cells. In severe COVID-19, NK cells show defects in virus control, cytokine production and cell-mediated cytotoxicity despite high expression of cytotoxic effector molecules. Single-cell RNA sequencing of NK cells over the time course of the COVID-19 disease spectrum reveals a distinct gene expression signature. Transcriptional networks of interferon-driven NK cell activation are superimposed by a dominant transforming growth factor-beta (TGF beta) response signature, with reduced expression of genes related to cell-cell adhesion, granule exocytosis and cell-mediated cytotoxicity. In severe COVID-19, serum levels of TGF beta peak during the first two weeks of infection, and serum obtained from these patients severely inhibits NK cell function in a TGF beta-dependent manner. Our data reveal that an untimely production of TGF beta is a hallmark of severe COVID-19 and may inhibit NK cell function and early control of the virus.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available