Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells
| العنوان: | Untimely TGFβ responses in COVID-19 limit antiviral functions of NK cells |
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| المؤلفون: | Gitta Anne Heinz, Josefine Radke, Sophie Mc Ewen, V. Moos, Jobst Roehmel, Tilmann Kallinich, Pawel Durek, Daniela Niemeyer, Leif G. Hanitsch, Florian Kurth, Thordis Hohnstein, Uwe Kölsch, Mario Witkowski, Philipp Nawrath, Marcus A. Mall, Frederik Heinrich, Leif E. Sander, Stefan Frischbutter, Mir-Farzin Mashreghi, Tom Aschman, Emanuela Marcenaro, Victor M. Corman, Edoardo Viviano, Sascha Treskatsch, Andreas Diefenbach, Marta Ferreira-Gomes, Marcus Maurer, Christian Meisel, Caroline Tizian, Robert Lorenz Chua, Claudia U. Duerr, Stefan Angermair, Andrey Kruglov, Helena Radbruch, Birgit Sawitzki, Silvia Zocche, Christian Conrad, Andreas Radbruch, Irene Mattiola, Joseph A. Trapani, Thomas Schneider, Christian Drosten, Terry Jones, Kristina Allers |
| المصدر: | Nature. 600:295-301 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Multidisciplinary, Innate immune system, Effector, medicine.medical_treatment, Cell, Innate lymphoid cell, Biology, Virus, Cell biology, medicine.anatomical_structure, Cytokine, Viral replication, medicine, Cytotoxic T cell |
| الوصف: | 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. |
| تدمد: | 1476-4687 0028-0836 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8ef4688f094e8d16773050add62ca69 https://doi.org/10.1038/s41586-021-04142-6 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e8ef4688f094e8d16773050add62ca69 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14764687 00280836 |
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