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Early Transcriptional Signature in Dendritic Cells and the Induction of Protective T Cell Responses Upon Immunization With VLPs Containing TLR Ligands—A Role for CCL2

Gomes, AC; Mohsen, MO; Mueller, JE; Leoratti, FMS; Cabral-Miranda, G; Bachmann, MF; (2019) Early Transcriptional Signature in Dendritic Cells and the Induction of Protective T Cell Responses Upon Immunization With VLPs Containing TLR Ligands—A Role for CCL2. Frontiers in Immunology , 10 , Article 1679. 10.3389/fimmu.2019.01679. Green open access

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Abstract

Inducing T cell responses by therapeutic vaccination requires appropriate activation of antigen presenting cells (APCs). The use of virus-like particles (VLPs) containing Toll-like receptor (TLR) ligands has demonstrated remarkable potential in activating APCs and modulating the immune response both for prophylactic vaccines as well as immunotherapy. Here, we employed VLPs associated to TLR ligands as tools to modulate cytotoxic response mediated by CD8+ T cells and provide further insight in the development of T cell-based immunotherapy. We have investigated the in vivo transcriptional signature in dendritic cells (DCs) from mice immunized with VLPs containing distinct classes of nucleic acid and correlated the expression patterns with the efficiency of induced T cell responses. We identified key pathways activated in DCs that are involved in the appropriated induction of T cell responses and show evidence for the modulatory effect of CCL2 in CD8+ T cells responses. These insights shed light on immune networks that are pivotal for the induction of potent cytotoxic T cell responses and identify key genes for appropriate DC activation and subsequent modulation of the adaptive immune response.

Type: Article
Title: Early Transcriptional Signature in Dendritic Cells and the Induction of Protective T Cell Responses Upon Immunization With VLPs Containing TLR Ligands—A Role for CCL2
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2019.01679
Publisher version: https://doi.org/10.3389/fimmu.2019.01679
Language: English
Additional information: Copyright © 2019 Gomes, Mohsen, Mueller, Leoratti, Cabral-Miranda and Bachmann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). 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.
Keywords: CCL2, CpG—oligonucleotides, T cell—DC interactions, VLP (virus-like particle), dendritic cell (DC)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10082169
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