Theobald, Sebastian J., Simonis, Alexander ORCID: 0000-0003-2945-9897, Georgomanolis, Theodoros ORCID: 0000-0002-4066-9257, Kreer, Christoph ORCID: 0000-0002-9140-9850, Zehner, Matthias, Eisfeld, Hannah S., Albert, Marie-Christine, Chhen, Jason, Motameny, Susanne, Erger, Florian ORCID: 0000-0002-2768-1702, Fischer, Julia ORCID: 0000-0001-6138-7454, Malin, Jakob J. ORCID: 0000-0002-2989-0436, Graeb, Jessica, Winter, Sandra, Pouikli, Andromachi ORCID: 0000-0003-1868-6875, David, Friederike ORCID: 0000-0001-9521-5669, Boell, Boris, Koehler, Philipp ORCID: 0000-0002-7386-7495, Vanshylla, Kanika ORCID: 0000-0003-4552-9170, Gruell, Henning, Suarez, Isabelle, Hallek, Michael, Faetkenheuer, Gerd, Jung, Norma, Cornely, Oliver A., Lehmann, Clara, Tessarz, Peter ORCID: 0000-0002-6953-9835, Altmueller, Janine, Nuernberg, Peter, Kashkar, Hamid, Klein, Florian, Koch, Manuel ORCID: 0000-0002-2962-7814 and Rybniker, Jan (2021). Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19. EMBO Mol. Med., 13 (8). HOBOKEN: WILEY. ISSN 1757-4684

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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-1 beta (IL-1 beta) in macrophages derived from COVID-19 patients but not in macrophages from healthy SARS-CoV-2 naive 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-1 beta 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Theobald, Sebastian J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simonis, AlexanderUNSPECIFIEDorcid.org/0000-0003-2945-9897UNSPECIFIED
Georgomanolis, TheodorosUNSPECIFIEDorcid.org/0000-0002-4066-9257UNSPECIFIED
Kreer, ChristophUNSPECIFIEDorcid.org/0000-0002-9140-9850UNSPECIFIED
Zehner, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eisfeld, Hannah S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Albert, Marie-ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chhen, JasonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Motameny, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erger, FlorianUNSPECIFIEDorcid.org/0000-0002-2768-1702UNSPECIFIED
Fischer, JuliaUNSPECIFIEDorcid.org/0000-0001-6138-7454UNSPECIFIED
Malin, Jakob J.UNSPECIFIEDorcid.org/0000-0002-2989-0436UNSPECIFIED
Graeb, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winter, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pouikli, AndromachiUNSPECIFIEDorcid.org/0000-0003-1868-6875UNSPECIFIED
David, FriederikeUNSPECIFIEDorcid.org/0000-0001-9521-5669UNSPECIFIED
Boell, BorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koehler, PhilippUNSPECIFIEDorcid.org/0000-0002-7386-7495UNSPECIFIED
Vanshylla, KanikaUNSPECIFIEDorcid.org/0000-0003-4552-9170UNSPECIFIED
Gruell, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suarez, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Faetkenheuer, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jung, NormaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cornely, Oliver A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lehmann, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tessarz, PeterUNSPECIFIEDorcid.org/0000-0002-6953-9835UNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kashkar, HamidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDorcid.org/0000-0002-2962-7814UNSPECIFIED
Rybniker, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-585537
DOI: 10.15252/emmm.202114150
Journal or Publication Title: EMBO Mol. Med.
Volume: 13
Number: 8
Date: 2021
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1757-4684
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NLRP3 INFLAMMASOME; INDUCTION; INFECTION; NEK7; RECOGNITION; EXPRESSION; IMMUNITYMultiple languages
Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58553

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