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Monocytes Elicit a Neutrophil-Independent Th1/Th17 Response Upon Immunization With a Mincle-Dependent Glycolipid Adjuvant

Successful subunit vaccination with recombinant proteins requires adjuvants. The glycolipid trehalose-dibehenate (TDB), a synthetic analog of the mycobacterial cord factor, potently induces Th1 and Th17 immune responses and is a candidate adjuvant for human immunization. TDB binds to the C-type lect...

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Autores principales: Desel, Christiane, Murray, Peter J., Lehmann, Christian H. K., Heger, Lukas, Christensen, Dennis, Andersen, Peter, Mack, Matthias, Dudziak, Diana, Lang, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108773/
https://www.ncbi.nlm.nih.gov/pubmed/35585969
http://dx.doi.org/10.3389/fimmu.2022.880474
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author Desel, Christiane
Murray, Peter J.
Lehmann, Christian H. K.
Heger, Lukas
Christensen, Dennis
Andersen, Peter
Mack, Matthias
Dudziak, Diana
Lang, Roland
author_facet Desel, Christiane
Murray, Peter J.
Lehmann, Christian H. K.
Heger, Lukas
Christensen, Dennis
Andersen, Peter
Mack, Matthias
Dudziak, Diana
Lang, Roland
author_sort Desel, Christiane
collection PubMed
description Successful subunit vaccination with recombinant proteins requires adjuvants. The glycolipid trehalose-dibehenate (TDB), a synthetic analog of the mycobacterial cord factor, potently induces Th1 and Th17 immune responses and is a candidate adjuvant for human immunization. TDB binds to the C-type lectin receptor Mincle and triggers Syk-Card9-dependent APC activation. In addition, interleukin (IL)-1 receptor/MyD88-dependent signaling is required for TDB adjuvanticity. The role of different innate immune cell types in adjuvant-stimulated Th1/Th17 responses is not well characterized. We investigated cell recruitment to the site of injection (SOI) and to the draining lymph nodes (dLNs) after immunization with the TDB containing adjuvant CAF01 in a protein-based vaccine. Recruitment of monocytes and neutrophils to the SOI and the dramatic increase in lymph node cellularity was partially dependent on both Mincle and MyD88. Despite their large numbers at the SOI, neutrophils were dispensable for the induction of Th1/Th17 responses. In contrast, CCR2-dependent monocyte recruitment was essential for the induction of Th1/Th17 cells. Transport of adjuvant to the dLN did not require Mincle, MyD88, or CCR2. Together, adjuvanticity conferred by monocytes can be separated at the cellular level from potential tissue damage by neutrophils.
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spelling pubmed-91087732022-05-17 Monocytes Elicit a Neutrophil-Independent Th1/Th17 Response Upon Immunization With a Mincle-Dependent Glycolipid Adjuvant Desel, Christiane Murray, Peter J. Lehmann, Christian H. K. Heger, Lukas Christensen, Dennis Andersen, Peter Mack, Matthias Dudziak, Diana Lang, Roland Front Immunol Immunology Successful subunit vaccination with recombinant proteins requires adjuvants. The glycolipid trehalose-dibehenate (TDB), a synthetic analog of the mycobacterial cord factor, potently induces Th1 and Th17 immune responses and is a candidate adjuvant for human immunization. TDB binds to the C-type lectin receptor Mincle and triggers Syk-Card9-dependent APC activation. In addition, interleukin (IL)-1 receptor/MyD88-dependent signaling is required for TDB adjuvanticity. The role of different innate immune cell types in adjuvant-stimulated Th1/Th17 responses is not well characterized. We investigated cell recruitment to the site of injection (SOI) and to the draining lymph nodes (dLNs) after immunization with the TDB containing adjuvant CAF01 in a protein-based vaccine. Recruitment of monocytes and neutrophils to the SOI and the dramatic increase in lymph node cellularity was partially dependent on both Mincle and MyD88. Despite their large numbers at the SOI, neutrophils were dispensable for the induction of Th1/Th17 responses. In contrast, CCR2-dependent monocyte recruitment was essential for the induction of Th1/Th17 cells. Transport of adjuvant to the dLN did not require Mincle, MyD88, or CCR2. Together, adjuvanticity conferred by monocytes can be separated at the cellular level from potential tissue damage by neutrophils. Frontiers Media S.A. 2022-05-02 /pmc/articles/PMC9108773/ /pubmed/35585969 http://dx.doi.org/10.3389/fimmu.2022.880474 Text en Copyright © 2022 Desel, Murray, Lehmann, Heger, Christensen, Andersen, Mack, Dudziak and Lang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Desel, Christiane
Murray, Peter J.
Lehmann, Christian H. K.
Heger, Lukas
Christensen, Dennis
Andersen, Peter
Mack, Matthias
Dudziak, Diana
Lang, Roland
Monocytes Elicit a Neutrophil-Independent Th1/Th17 Response Upon Immunization With a Mincle-Dependent Glycolipid Adjuvant
title Monocytes Elicit a Neutrophil-Independent Th1/Th17 Response Upon Immunization With a Mincle-Dependent Glycolipid Adjuvant
title_full Monocytes Elicit a Neutrophil-Independent Th1/Th17 Response Upon Immunization With a Mincle-Dependent Glycolipid Adjuvant
title_fullStr Monocytes Elicit a Neutrophil-Independent Th1/Th17 Response Upon Immunization With a Mincle-Dependent Glycolipid Adjuvant
title_full_unstemmed Monocytes Elicit a Neutrophil-Independent Th1/Th17 Response Upon Immunization With a Mincle-Dependent Glycolipid Adjuvant
title_short Monocytes Elicit a Neutrophil-Independent Th1/Th17 Response Upon Immunization With a Mincle-Dependent Glycolipid Adjuvant
title_sort monocytes elicit a neutrophil-independent th1/th17 response upon immunization with a mincle-dependent glycolipid adjuvant
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108773/
https://www.ncbi.nlm.nih.gov/pubmed/35585969
http://dx.doi.org/10.3389/fimmu.2022.880474
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