Le Bert, N;
Chain, BM;
Rook, G;
Noursadeghi, M;
(2011)
DC Priming by M. vaccae Inhibits Th2 Responses in Contrast to Specific TLR2 Priming and Is Associated with Selective Activation of the CREB Pathway.
PLOS ONE
, 6
(4)
, Article e18346. 10.1371/journal.pone.0018346.
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Abstract
The environmental mycobacterium, M. vaccae has been used in mouse models to support the contemporary hygiene hypothesis that non-pathogenic microorganisms reduce allergy associated T helper (Th)2 responses and inflammatory diseases by augmenting regulatory T cells. However, data for human models and possible mechanisms are limited. We tested the effect of innate immune interactions between human DC and M. vaccae on DC-dependent T cell responses. M. vaccae activation of DC via Toll like receptor (TLR)2 was compared to a specific TLR2 ligand (Pam(3)CSK4) and alternative stimulation with a TLR4 ligand (LPS). M. vaccae induced DC dependent inhibition of Th2 responses, in contrast to Pam(3)CSK4, which had the opposite effect and LPS, which had no polarizing effect. DC maturation, gene expression and cytokine production, in response to each stimulus did not correlate with the specific functional effects. Comparable DC transcriptional responses to M. vaccae and Pam(3)CSK4 suggested that TLR2 mediated transcriptional regulation was not sufficient for inhibition of Th2 responses. Transcription factor enrichment analysis and assessment of signaling events, implicated a role for selective early activation of the CREB pathway by M. vaccae. Further study of the CREB pathway may provide novel insight into the molecular mechanisms of DC-dependent T cell polarization.
| Type: | Article |
|---|---|
| Title: | DC Priming by M. vaccae Inhibits Th2 Responses in Contrast to Specific TLR2 Priming and Is Associated with Selective Activation of the CREB Pathway |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0018346 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0018346 |
| Language: | English |
| Additional information: | © 2011 Le Bert et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was funded by an EC grant through the Marie Curie Early Stage Training Site GALTRAIN (project MEST-CT-2005-020524), supported by a Wellcome Trust fellowship (WT077161MA) to MN and the National Institute for Health Research UCLH/UCL Comprehensive Biomedical Research Centre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. GR is a shareholder of Silence Therapeutics, which owns intellectual property related to M. vaccae. This intellectual property has been licensed to Immodulon with which GR has no financial links. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. |
| Keywords: | KILLED MYCOBACTERIUM-VACCAE, CHRONIC INFLAMMATORY DISORDERS, TOLL-LIKE RECEPTOR-2, REGULATORY T-CELLS, DENDRITIC CELLS, ATOPIC-DERMATITIS, BINDING PROTEIN, MACROPHAGE ACTIVATION, IMMUNE-RESPONSES, MITE ALLERGEN |
| 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/1304568 |
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