EMBO Molecular Medicine (Aug 2021)
Long‐lived macrophage reprogramming drives spike protein‐mediated inflammasome activation in COVID‐19
- Sebastian J Theobald,
- Alexander Simonis,
- Theodoros Georgomanolis,
- Christoph Kreer,
- Matthias Zehner,
- Hannah S Eisfeld,
- Marie‐Christine Albert,
- 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
Affiliations
- Sebastian J Theobald
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Alexander Simonis
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Theodoros Georgomanolis
- Faculty of Medicine and University Hospital of Cologne Cologne Center for Genomics (CCG) University of Cologne Cologne Germany
- Christoph Kreer
- Laboratory of Experimental Immunology Institute of Virology Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Matthias Zehner
- Laboratory of Experimental Immunology Institute of Virology Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Hannah S Eisfeld
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Marie‐Christine Albert
- Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD) University of Cologne Cologne Germany
- Jason Chhen
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Susanne Motameny
- Faculty of Medicine and University Hospital of Cologne Cologne Center for Genomics (CCG) University of Cologne Cologne Germany
- Florian Erger
- Faculty of Medicine and University Hospital of Cologne Cologne Center for Genomics (CCG) University of Cologne Cologne Germany
- Julia Fischer
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Jakob J Malin
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Jessica Gräb
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Sandra Winter
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Andromachi Pouikli
- Max Planck Research Group “Chromatin and Ageing” Max Planck Institute for Biology of Ageing Cologne Germany
- Friederike David
- Faculty of Medicine and University Hospital of Cologne Cologne Center for Genomics (CCG) University of Cologne Cologne Germany
- Boris Böll
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Philipp Koehler
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Kanika Vanshylla
- Laboratory of Experimental Immunology Institute of Virology Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Henning Gruell
- Laboratory of Experimental Immunology Institute of Virology Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Isabelle Suárez
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Michael Hallek
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Gerd Fätkenheuer
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Norma Jung
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Oliver A Cornely
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Clara Lehmann
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Peter Tessarz
- Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD) University of Cologne Cologne Germany
- Janine Altmüller
- Faculty of Medicine and University Hospital of Cologne Cologne Center for Genomics (CCG) University of Cologne Cologne Germany
- Peter Nürnberg
- Faculty of Medicine and University Hospital of Cologne Center for Molecular Medicine Cologne (CMMC) University of Cologne Cologne Germany
- Hamid Kashkar
- Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases (CECAD) University of Cologne Cologne Germany
- Florian Klein
- Laboratory of Experimental Immunology Institute of Virology Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- Manuel Koch
- Medical Faculty Institute for Dental Research and Oral Musculoskeletal Biology University of Cologne Cologne Germany
- Jan Rybniker
- Department I of Internal Medicine Faculty of Medicine and University Hospital of Cologne University of Cologne Cologne Germany
- DOI
- https://doi.org/10.15252/emmm.202114150
- Journal volume & issue
-
Vol. 13,
no. 8
pp. n/a – n/a
Abstract
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
