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Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS‐CoV‐2 mRNA vaccination

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 prime...

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Autores principales: Theobald, Sebastian J, Simonis, Alexander, Mudler, Julie M, Göbel, Ulrike, Acton, Richard, Kohlhas, Viktoria, Albert, Marie‐Christine, Hellmann, Anna‐Maria, Malin, Jakob J, Winter, Sandra, Hallek, Michael, Walczak, Henning, Nguyen, Phuong‐Hien, Koch, Manuel, Rybniker, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349614/
https://www.ncbi.nlm.nih.gov/pubmed/35785445
http://dx.doi.org/10.15252/emmm.202215888
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author Theobald, Sebastian J
Simonis, Alexander
Mudler, Julie M
Göbel, Ulrike
Acton, Richard
Kohlhas, Viktoria
Albert, Marie‐Christine
Hellmann, Anna‐Maria
Malin, Jakob J
Winter, Sandra
Hallek, Michael
Walczak, Henning
Nguyen, Phuong‐Hien
Koch, Manuel
Rybniker, Jan
author_facet Theobald, Sebastian J
Simonis, Alexander
Mudler, Julie M
Göbel, Ulrike
Acton, Richard
Kohlhas, Viktoria
Albert, Marie‐Christine
Hellmann, Anna‐Maria
Malin, Jakob J
Winter, Sandra
Hallek, Michael
Walczak, Henning
Nguyen, Phuong‐Hien
Koch, Manuel
Rybniker, Jan
author_sort Theobald, Sebastian J
collection PubMed
description 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.
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spelling pubmed-93496142022-08-04 Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS‐CoV‐2 mRNA vaccination Theobald, Sebastian J Simonis, Alexander Mudler, Julie M Göbel, Ulrike Acton, Richard Kohlhas, Viktoria Albert, Marie‐Christine Hellmann, Anna‐Maria Malin, Jakob J Winter, Sandra Hallek, Michael Walczak, Henning Nguyen, Phuong‐Hien Koch, Manuel Rybniker, Jan EMBO Mol Med Articles 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. John Wiley and Sons Inc. 2022-07-04 /pmc/articles/PMC9349614/ /pubmed/35785445 http://dx.doi.org/10.15252/emmm.202215888 Text en © 2022 The Authors. Published under the terms of the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Theobald, Sebastian J
Simonis, Alexander
Mudler, Julie M
Göbel, Ulrike
Acton, Richard
Kohlhas, Viktoria
Albert, Marie‐Christine
Hellmann, Anna‐Maria
Malin, Jakob J
Winter, Sandra
Hallek, Michael
Walczak, Henning
Nguyen, Phuong‐Hien
Koch, Manuel
Rybniker, Jan
Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS‐CoV‐2 mRNA vaccination
title Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS‐CoV‐2 mRNA vaccination
title_full Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS‐CoV‐2 mRNA vaccination
title_fullStr Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS‐CoV‐2 mRNA vaccination
title_full_unstemmed Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS‐CoV‐2 mRNA vaccination
title_short Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS‐CoV‐2 mRNA vaccination
title_sort spleen tyrosine kinase mediates innate and adaptive immune crosstalk in sars‐cov‐2 mrna vaccination
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349614/
https://www.ncbi.nlm.nih.gov/pubmed/35785445
http://dx.doi.org/10.15252/emmm.202215888
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