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Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19

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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. and Simonis, A. and Georgomanolis, T. and Kreer, C. and Zehner, M. and Eisfeld, H.S. and Albert, M.C. and Chhen, J. and Motameny, S. and Erger, F. and Fischer, J. and Malin, J.J. and Gräb, J. and Winter, S. and Pouikli, A. and David, F. and Böll, B. and Koehler, P. and Vanshylla, K. and Gruell, H. and Suárez, I. and Hallek, M. and Fätkenheuer, G. and Jung, N. and Cornely, O.A. and Lehmann, C. and Tessarz, P. and Altmüller, J. and Nürnberg, P. and Kashkar, H. and Klein, F. and 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: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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