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Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naïve subjects
The protection against tuberculosis induced by the Bacille Calmette Guérin (BCG) vaccine is unpredictable. In our previous study, altered DNA methylation pattern in peripheral blood mononuclear cells (PBMCs) in response to BCG was observed in a subgroup of individuals, whose macrophages killed mycob...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557603/ https://www.ncbi.nlm.nih.gov/pubmed/31010371 http://dx.doi.org/10.1080/15592294.2019.1603963 |
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author | Das, Jyotirmoy Verma, Deepti Gustafsson, Mika Lerm, Maria |
author_facet | Das, Jyotirmoy Verma, Deepti Gustafsson, Mika Lerm, Maria |
author_sort | Das, Jyotirmoy |
collection | PubMed |
description | The protection against tuberculosis induced by the Bacille Calmette Guérin (BCG) vaccine is unpredictable. In our previous study, altered DNA methylation pattern in peripheral blood mononuclear cells (PBMCs) in response to BCG was observed in a subgroup of individuals, whose macrophages killed mycobacteria effectively (‘responders’). These macrophages also showed production of Interleukin-1β (IL-1β) in response to mycobacterial stimuli before vaccination. Here, we hypothesized that the propensity to respond to the BCG vaccine is reflected in the DNA methylome. We mapped the differentially methylated genes (DMGs) in PBMCs isolated from responders/non-responders at the time point before vaccination aiming to identify possible predictors of BCG responsiveness. We identified 43 DMGs and subsequent bioinformatic analyses showed that these were enriched for actin-modulating pathways, predicting differences in phagocytosis. This could be validated by experiments showing that phagocytosis of mycobacteria, which is an event preceding mycobacteria-induced IL-1β production, was strongly correlated with the DMG pattern. |
format | Online Article Text |
id | pubmed-6557603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-65576032019-06-19 Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naïve subjects Das, Jyotirmoy Verma, Deepti Gustafsson, Mika Lerm, Maria Epigenetics Research Paper The protection against tuberculosis induced by the Bacille Calmette Guérin (BCG) vaccine is unpredictable. In our previous study, altered DNA methylation pattern in peripheral blood mononuclear cells (PBMCs) in response to BCG was observed in a subgroup of individuals, whose macrophages killed mycobacteria effectively (‘responders’). These macrophages also showed production of Interleukin-1β (IL-1β) in response to mycobacterial stimuli before vaccination. Here, we hypothesized that the propensity to respond to the BCG vaccine is reflected in the DNA methylome. We mapped the differentially methylated genes (DMGs) in PBMCs isolated from responders/non-responders at the time point before vaccination aiming to identify possible predictors of BCG responsiveness. We identified 43 DMGs and subsequent bioinformatic analyses showed that these were enriched for actin-modulating pathways, predicting differences in phagocytosis. This could be validated by experiments showing that phagocytosis of mycobacteria, which is an event preceding mycobacteria-induced IL-1β production, was strongly correlated with the DMG pattern. Taylor & Francis 2019-04-22 /pmc/articles/PMC6557603/ /pubmed/31010371 http://dx.doi.org/10.1080/15592294.2019.1603963 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Das, Jyotirmoy Verma, Deepti Gustafsson, Mika Lerm, Maria Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naïve subjects |
title | Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naïve subjects |
title_full | Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naïve subjects |
title_fullStr | Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naïve subjects |
title_full_unstemmed | Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naïve subjects |
title_short | Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naïve subjects |
title_sort | identification of dna methylation patterns predisposing for an efficient response to bcg vaccination in healthy bcg-naïve subjects |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557603/ https://www.ncbi.nlm.nih.gov/pubmed/31010371 http://dx.doi.org/10.1080/15592294.2019.1603963 |
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