Theobald, Sebastian J., Simonis, Alexander ORCID: 0000-0003-2945-9897, Mudler, Julie M., Goebel, Ulrike, Acton, Richard, Kohlhas, Viktoria, Albert, Marie-Christine, Hellmann, Anna-Maria, Malin, Jakob J. ORCID: 0000-0002-2989-0436, Winter, Sandra, Hallek, Michael ORCID: 0000-0002-7425-4455, Walczak, Henning, Koch, Manuel ORCID: 0000-0002-2962-7814 and Rybniker, Jan (2022). Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS-CoV-2 mRNA vaccination. EMBO Mol. Med., 14 (8). HOBOKEN: WILEY. ISSN 1757-4684

Full text not available from this repository.

Abstract

Durable cell-mediated immune responses require efficient innate immune signaling and the release of pro-inflammatory cytokines. How precisely mRNA vaccines trigger innate immune cells for shaping antigen specific adaptive immunity remains unknown. Here, we show that SARS-CoV-2 mRNA vaccination primes human monocyte-derived macrophages for activation of the NLRP3 inflammasome. Spike protein exposed macrophages undergo NLRP3-driven pyroptotic cell death and subsequently secrete mature interleukin-1 beta. These effects depend on activation of spleen tyrosine kinase (SYK) coupled to C-type lectin receptors. Using autologous cocultures, we show that SYK and NLRP3 orchestrate macrophage-driven activation of effector memory T cells. Furthermore, vaccination-induced macrophage priming can be enhanced with repetitive antigen exposure providing a rationale for prime-boost concepts to augment innate immune signaling in SARS-CoV-2 vaccination. Collectively, these findings identify SYK as a regulatory node capable of differentiating between primed and unprimed macrophages, which modulate spike protein-specific T cell responses.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Theobald, Sebastian J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simonis, AlexanderUNSPECIFIEDorcid.org/0000-0003-2945-9897UNSPECIFIED
Mudler, Julie M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goebel, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Acton, RichardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kohlhas, ViktoriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Albert, Marie-ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hellmann, Anna-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malin, Jakob J.UNSPECIFIEDorcid.org/0000-0002-2989-0436UNSPECIFIED
Winter, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hallek, MichaelUNSPECIFIEDorcid.org/0000-0002-7425-4455UNSPECIFIED
Walczak, HenningUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDorcid.org/0000-0002-2962-7814UNSPECIFIED
Rybniker, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-678973
DOI: 10.15252/emmm.202215888
Journal or Publication Title: EMBO Mol. Med.
Volume: 14
Number: 8
Date: 2022
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1757-4684
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INFLAMMASOME; RECOGNITION; MEMORY; VIRUSMultiple languages
Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/67897

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item