Academic Journal
Long‐lived macrophage reprogramming drives spike protein‐mediated inflammasome activation in COVID‐19
| العنوان: | Long‐lived macrophage reprogramming drives spike protein‐mediated inflammasome activation in COVID‐19 |
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| المؤلفون: | Sebastian J Theobald, Alexander Simonis, Theodoros Georgomanolis, Christoph Kreer, Matthias Zehner, Hannah S Eisfeld, Marie‐Christine Albert, Jason Chhen, Susanne Motameny, Florian Erger, Julia Fischer, Jakob J Malin, Jessica Gräb, Sandra Winter, Andromachi Pouikli, Friederike David, Boris Böll, Philipp Koehler, Kanika Vanshylla, Henning Gruell, Isabelle Suárez, Michael Hallek, Gerd Fätkenheuer, Norma Jung, Oliver A Cornely, Clara Lehmann, Peter Tessarz, Janine Altmüller, Peter Nürnberg, Hamid Kashkar, Florian Klein, Manuel Koch, Jan Rybniker |
| المصدر: | EMBO Molecular Medicine, Vol 13, Iss 8, Pp 1-20 (2021) |
| بيانات النشر: | Springer Nature, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | inflammasome, innate immunity, macrophage, NLRP3, SARS‐CoV‐2, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract Innate immunity triggers responsible for viral control or hyperinflammation in COVID‐19 are largely unknown. Here we show that the SARS‐CoV‐2 spike protein (S‐protein) primes inflammasome formation and release of mature interleukin‐1β (IL‐1β) in macrophages derived from COVID‐19 patients but not in macrophages from healthy SARS‐CoV‐2 naïve individuals. Furthermore, longitudinal analyses reveal robust S‐protein‐driven inflammasome activation in macrophages isolated from convalescent COVID‐19 patients, which correlates with distinct epigenetic and gene expression signatures suggesting innate immune memory after recovery from COVID‐19. Importantly, we show that S‐protein‐driven IL‐1β secretion from patient‐derived macrophages requires non‐specific monocyte pre‐activation in vivo to trigger NLRP3‐inflammasome signaling. Our findings reveal that SARS‐CoV‐2 infection causes profound and long‐lived reprogramming of macrophages resulting in augmented immunogenicity of the SARS‐CoV‐2 S‐protein, a major vaccine antigen and potent driver of adaptive and innate immune signaling. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4676 1757-4684 |
| Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
| DOI: | 10.15252/emmm.202114150 |
| URL الوصول: | https://doaj.org/article/2445731f5efd43e7bf9dcd749ffcad99 |
| رقم الانضمام: | edsdoj.2445731f5efd43e7bf9dcd749ffcad99 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574676 17574684 |
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| DOI: | 10.15252/emmm.202114150 |