Open AccessSpleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS‐CoV‐2 mRNA vaccination
Author(s) -
Theobald Sebastian J,
Simonis Alexander,
Mudler Julie M,
Göbel Ulrike,
Acton Richard,
Kohlhas Viktoria,
Albert MarieChristine,
Hellmann AnnaMaria,
Malin Jakob J,
Winter Sandra,
Hallek Michael,
Walczak Henning,
Nguyen PhuongHien,
Koch Manuel,
Rybniker Jan
Publication year - 2022
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202215888
Subject(s) - innate immune system , vaccination , crosstalk , virology , biology , spleen , immune system , acquired immune system , tyrosine kinase , messenger rna , immunology , signal transduction , microbiology and biotechnology , gene , genetics , physics , optics
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‐1β. 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.