Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS-CoV-2 mRNA vaccination.
EMBO Mol Med
; 14(8): e15888, 2022 08 08.
Article
in English
| MEDLINE | ID: covidwho-1918174
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-1ß. 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
NLR Family, Pyrin Domain-Containing 3 Protein
/
COVID-19
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
EMBO Mol Med
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
Affiliation country:
Emmm.202215888
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