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Identification of DNA methylation patterns predisposing for an efficient response to BCG vaccination in healthy BCG-naive subjects
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-5092-9892
2019 (English)In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 14, no 6, p. 589-601Article in journal (Refereed) Published
Abstract [en]

The protection against tuberculosis induced by the Bacille Calmette Guerin (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-1 beta (IL-1 beta) 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-1 beta production, was strongly correlated with the DMG pattern.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS INC , 2019. Vol. 14, no 6, p. 589-601
Keywords [en]
DNA methylation; BCG-vaccination; phagocytosis; actin regulation; Mycobacterium tuberculosis; Tuberculosis
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:liu:diva-158857DOI: 10.1080/15592294.2019.1603963ISI: 000471388000001PubMedID: 31010371OAI: oai:DiVA.org:liu-158857DiVA, id: diva2:1337522
Note

Funding Agencies|Hjart-Lungfonden [20150709]; Vetenskapsradet [2012-3349]

Available from: 2019-07-15 Created: 2019-07-15 Last updated: 2019-07-25

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Das, JyotirmoyVerma, DeeptiGustafsson, MikaLerm, Maria
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