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Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I
DC-SIGN is an antigen uptake receptor expressed on dendritic cells (DCs) with specificity for glycans present on a broad variety of pathogens and is capable of directing its cargo to MHC-I and MHC-II pathways for the induction of CD8(+) and CD4(+) T cell responses, respectively. Therefore, DC-SIGN i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010527/ https://www.ncbi.nlm.nih.gov/pubmed/29963041 http://dx.doi.org/10.3389/fimmu.2018.01231 |
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author | Horrevorts, Sophie K. Duinkerken, Sanne Bloem, Karien Secades, Pablo Kalay, Hakan Musters, René J. van Vliet, Sandra J. García-Vallejo, Juan J. van Kooyk, Yvette |
author_facet | Horrevorts, Sophie K. Duinkerken, Sanne Bloem, Karien Secades, Pablo Kalay, Hakan Musters, René J. van Vliet, Sandra J. García-Vallejo, Juan J. van Kooyk, Yvette |
author_sort | Horrevorts, Sophie K. |
collection | PubMed |
description | DC-SIGN is an antigen uptake receptor expressed on dendritic cells (DCs) with specificity for glycans present on a broad variety of pathogens and is capable of directing its cargo to MHC-I and MHC-II pathways for the induction of CD8(+) and CD4(+) T cell responses, respectively. Therefore, DC-SIGN is a very promising target for the delivery of antigen for anti-cancer vaccination. Although the endocytic route leading to MHC-II presentation is characterized to a large extent, the mechanisms controlling DC-SIGN targeted cross-presentation of exogenous peptides on MHC-I, are not completely resolved yet. In this paper, we used imaging flow cytometry and antigen-specific CD8(+) T cells to investigate the intracellular fate of DC-SIGN and its cargo in human DCs. Our data demonstrates that immature DCs and toll-like receptor 4 (TLR4) stimulated DCs had similar internalization capacity and were both able to cross-present antigen targeted via DC-SIGN. Interestingly, simultaneous triggering of TLR4 and DC-SIGN on DCs resulted in the translocation of cargo to the cytosol, leading to proteasome-dependent processing and increased CD8(+) T cell activation. Understanding the dynamics of DC-SIGN-mediated uptake and processing is essential for the design of optimal DC-SIGN-targeting vaccination strategies aimed at enhancing CD8(+) T cell responses. |
format | Online Article Text |
id | pubmed-6010527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60105272018-06-29 Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I Horrevorts, Sophie K. Duinkerken, Sanne Bloem, Karien Secades, Pablo Kalay, Hakan Musters, René J. van Vliet, Sandra J. García-Vallejo, Juan J. van Kooyk, Yvette Front Immunol Immunology DC-SIGN is an antigen uptake receptor expressed on dendritic cells (DCs) with specificity for glycans present on a broad variety of pathogens and is capable of directing its cargo to MHC-I and MHC-II pathways for the induction of CD8(+) and CD4(+) T cell responses, respectively. Therefore, DC-SIGN is a very promising target for the delivery of antigen for anti-cancer vaccination. Although the endocytic route leading to MHC-II presentation is characterized to a large extent, the mechanisms controlling DC-SIGN targeted cross-presentation of exogenous peptides on MHC-I, are not completely resolved yet. In this paper, we used imaging flow cytometry and antigen-specific CD8(+) T cells to investigate the intracellular fate of DC-SIGN and its cargo in human DCs. Our data demonstrates that immature DCs and toll-like receptor 4 (TLR4) stimulated DCs had similar internalization capacity and were both able to cross-present antigen targeted via DC-SIGN. Interestingly, simultaneous triggering of TLR4 and DC-SIGN on DCs resulted in the translocation of cargo to the cytosol, leading to proteasome-dependent processing and increased CD8(+) T cell activation. Understanding the dynamics of DC-SIGN-mediated uptake and processing is essential for the design of optimal DC-SIGN-targeting vaccination strategies aimed at enhancing CD8(+) T cell responses. Frontiers Media S.A. 2018-06-14 /pmc/articles/PMC6010527/ /pubmed/29963041 http://dx.doi.org/10.3389/fimmu.2018.01231 Text en Copyright © 2018 Horrevorts, Duinkerken, Bloem, Secades, Kalay, Musters, van Vliet, García-Vallejo and van Kooyk. 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 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 Horrevorts, Sophie K. Duinkerken, Sanne Bloem, Karien Secades, Pablo Kalay, Hakan Musters, René J. van Vliet, Sandra J. García-Vallejo, Juan J. van Kooyk, Yvette Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I |
title | Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I |
title_full | Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I |
title_fullStr | Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I |
title_full_unstemmed | Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I |
title_short | Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I |
title_sort | toll-like receptor 4 triggering promotes cytosolic routing of dc-sign-targeted antigens for presentation on mhc class i |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010527/ https://www.ncbi.nlm.nih.gov/pubmed/29963041 http://dx.doi.org/10.3389/fimmu.2018.01231 |
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