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Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cellsстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Witkowski Mario, Tizian Caroline, Ferreira-Gomes Marta, Niemeyer Daniela, Jones Terry C., Heinrich Frederik, Frischbutter Stefan, Angermair Stefan, Hohnstein Thordis, Mattiola Irene, Nawrath Philipp, Ewen Sophie Mc, Zocche Silvia, Viviano Edoardo, Heinz Gitta Anne, Maurer Marcus, Kölsch Uwe, Chua Robert Lorenz, Aschman Tom, Meisel Christian, Radke Josefine, Sawitzki Birgit, Roehmel Jobst, Allers Kristina, Moos Verena, Schneider Thomas, Hanitsch Leif, Mall Marcus A., Conrad Christian, Radbruch Helena, Duerr Claudia U., Trapani Joseph A., Marcenaro Emanuela, Kallinich Tilmann, Corman Victor M., Kurth Florian, Sander Leif Erik, Drosten Christian, Treskatsch Sascha, Durek Pawel, Kruglov Andrey, Radbruch Andreas, Mashreghi Mir-Farzin, Diefenbach Andreas
- Журнал: Nature
- Год издания: 2021
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- DOI: 10.1038/s41586-021-04142-6
- Аннотация: SARS-CoV-2 is a single-stranded RNA virus that causes coronavirus disease 2019 (COVID-19). Given its acute and often self-limiting course, components of the innate immune system are likely central in controlling virus replication thereby determining clinical outcome. Natural killer (NK) cells are innate lymphocytes with notable activity against a broad range of viruses, including RNA viruses1,2. NK cell function may be altered during COVID-19 despite increased representation of NK cells with an activated and ‘adaptive’ phenotype3,4. Here we show that viral load decline 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 remarkable defects in virus control, cytokine production and cell-mediated cytotoxicity despite high expression of cytotoxic effector molecules. Single-cell RNA-sequencing (scRNA-seq) of NK cells along the time course of the entire COVID-19 disease spectrum reveals a unique gene expression signature. Transcriptional networks of interferon-driven NK cell activation are superimposed by a dominant TGFβ 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 TGFβ peak during the first 2 weeks of infection, and serum obtained from these patients profoundly inhibits NK cell function in a TGFβ-dependent manner. Our data reveal that untimely production of TGFβ is a hallmark of severe COVID-19 and may inhibit NK cell function and early virus control.
- Добавил в систему: Круглов Андрей Алексеевич