Open AccessLong‐lived macrophage reprogramming drives spike protein‐mediated inflammasome activation in COVID‐19
Author(s) -
Theobald Sebastian J,
Simonis Alexander,
Georgomanolis Theodoros,
Kreer Christoph,
Zehner Matthias,
Eisfeld Hannah S,
Albert MarieChristine,
Chhen Jason,
Motameny Susanne,
Erger Florian,
Fischer Julia,
Malin Jakob J,
Gräb Jessica,
Winter Sandra,
Pouikli Andromachi,
David Friederike,
Böll Boris,
Koehler Philipp,
Vanshylla Kanika,
Gruell Henning,
Suárez Isabelle,
Hallek Michael,
Fätkenheuer Gerd,
Jung Norma,
Cornely Oliver A,
Lehmann Clara,
Tessarz Peter,
Altmüller Janine,
Nürnberg Peter,
Kashkar Hamid,
Klein Florian,
Koch Manuel,
Rybniker Jan
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202114150
Subject(s) - inflammasome , innate immune system , biology , immunogenicity , acquired immune system , immune system , reprogramming , microbiology and biotechnology , immunology , immunity , macrophage , inflammation , cell , in vitro , genetics
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.