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| Item Type: | Article |
|---|---|
| Title: | Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19 |
| Creators Name: | Theobald, S.J., Simonis, A., Georgomanolis, T., Kreer, C., Zehner, M., Eisfeld, H.S., Albert, M.C., Chhen, J., Motameny, S., Erger, F., Fischer, J., Malin, J.J., Gräb, J., Winter, S., Pouikli, A., David, F., Böll, B., Koehler, P., Vanshylla, K., Gruell, H., Suárez, I., Hallek, M., Fätkenheuer, G., Jung, N., Cornely, O.A., Lehmann, C., Tessarz, P., Altmüller, J., Nürnberg, P., Kashkar, H., Klein, F., Koch, M. and Rybniker, J. |
| 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. |
| Keywords: | Inflammasomes, Innate Immunity, Macrophages, NLRP3, SARS-CoV-2, COVID-19, Innate Immunity, Interleukin-1beta, Pyrin Domain-Containing 3 Protein NLR Family, Coronavirus Spike Glycoprotein |
| Source: | EMBO Molecular Medicine |
| ISSN: | 1757-4676 |
| Publisher: | EMBO Press / Wiley |
| Volume: | 13 |
| Number: | 8 |
| Page Range: | e14150 |
| Date: | 9 August 2021 |
| Official Publication: | https://doi.org/10.15252/emmm.202114150 |
| PubMed: | View item in PubMed |
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