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| Item Type: | Article |
|---|---|
| Title: | Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19 |
| Creators: |
Theobald, S.J., Simonis, A.  ORCID: https://orcid.org/0000-0003-2945-9897, Georgomanolis, T. ORCID: https://orcid.org/0000-0002-4066-9257, Kreer, C. ORCID: https://orcid.org/0000-0002-9140-9850, Zehner, M., Eisfeld, H.S., Albert, M.C., Chhen, J., Motameny, S. ORCID: https://orcid.org/0000-0003-1186-1108, Erger, F., Fischer, J. ORCID: https://orcid.org/0000-0001-6138-7454, Malin, J.J. ORCID: https://orcid.org/0000-0002-2989-0436, Gräb, J., Winter, S., Pouikli, A., David, F. ORCID: https://orcid.org/0000-0001-9521-5669, Böll, B., Koehler, P., Vanshylla, K., Gruell, H. ORCID: https://orcid.org/0000-0002-0725-7138, Suárez, I., Hallek, M., Fätkenheuer, G., Jung, N., Cornely, O.A., Lehmann, C., Tessarz, P. ORCID: https://orcid.org/0000-0002-6953-9835, Altmüller, J. ORCID: https://orcid.org/0000-0003-4372-1521, Nürnberg, P., Kashkar, H., Klein, F., Koch, M. and Rybniker, J. ORCID: https://orcid.org/0000-0001-8351-2690
|
| 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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