Original Research ARTICLE
Early transcriptional signature in dendritic cells and the induction of protective T cell responses upon immunisation with VLPs containing TLR ligands – a role for CCL2
- 1University of Oxford, United Kingdom
- 2Bern University Hospital, Switzerland
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 immunised 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.
Keywords: VLP (virus-like particle), CpG - oligonucleotides, dendritic cell (DC), T cell - DC interactions, CCL2
Received: 03 Mar 2019;
Accepted: 04 Jul 2019.
Edited by:Lee M. Wetzler, School of Medicine, Boston University, United States
Reviewed by:Beatrice Jahn-Schmid, Medical University of Vienna, Austria
Michael Schotsaert, Icahn School of Medicine at Mount Sinai, United States
Copyright: © 2019 Cruz Gomes, Mohsen, Muller, Leoratti, Cabral-Miranda and Bachmann. 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.
* Correspondence: Dr. Ariane Cruz Gomes, University of Oxford, Oxford, OX1 2JD, England, United Kingdom, firstname.lastname@example.org