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

• DOI: 10.15252/emmm.202114150
• Publication Date: 2021-06-16T10:35:06Z
• Authors: Sebastian J Theobald; Alexander Simonis; Theodoros Georgom...; Christoph Kreer; Matthias Zehner; Hannah S Eisfeld; Marie‐Christine A...; 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
• Keywords: Reprogramming

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) macrophages derived from patients but not healthy naïve individuals. Furthermore, longitudinal analyses reveal robust S-protein-driven activation isolated convalescent patients, which correlates with distinct epigenetic gene expression signatures suggesting innate immune memory after recovery COVID-19. Importantly, IL-1β secretion patient-derived requires non-specific monocyte pre-activation vivo to trigger NLRP3-inflammasome signaling. Our findings infection causes profound long-lived reprogramming resulting augmented immunogenicity S-protein, a major vaccine antigen potent driver adaptive