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. SARS‐CoV‐2 infection leads to hyperinflammatory syndromes in a subset of patients. We show that human primary macrophages require genome‐wide transcriptional modifications for pro‐inflammatory signaling upon stimulation with the SARS‐CoV‐2 surface glycoprotein (S‐protein).
【저자키워드】 immunology, Macrophage, Innate immunity, SARS‐CoV‐2, Microbiology, Virology & Host Pathogen Interaction, Inflammasome, NLRP3, 【초록키워드】 adaptive, Immunity, Spike protein, monocyte, COVID‐19, SARS‐CoV‐2, Surface glycoprotein, Hyperinflammatory syndrome, hyperinflammation, convalescent, in vivo, Epigenetic, patients, innate immune memory, longitudinal analysis, Signaling, innate immune, Innate, Trigger, COVID‐19 patients, naïve individuals, secretion, inflammasome activation, SARS‐CoV‐2 infection, gene expression signature, viral control, Modification, vaccine antigen, transcriptional, robust, responsible, resulting, healthy, cause, subset, COVID‐19 patient, 【제목키워드】 COVID‐19, inflammasome activation,