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Anti-mycobacterial activity correlates with altered DNA methylation pattern in immune cells from BCG-vaccinated subjects
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. 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.
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 12305Article in journal (Refereed) Published
Abstract [en]

The reason for the largely variable protective effect against TB of the vaccine Bacille Calmette-Guerin (BCG) is not understood. In this study, we investigated whether epigenetic mechanisms are involved in the response of immune cells to the BCG vaccine. We isolated peripheral blood mononuclear cells (PBMCs) from BCG-vaccinated subjects and performed global DNA methylation analysis in combination with functional assays representative of innate immunity against Mycobacterium tuberculosis infection. Enhanced containment of replication was observed in monocyte-derived macrophages from a subgroup of BCG-vaccinated individuals (identified as responders). A stable and robust differential DNA methylation pattern in response to BCG could be observed in PBMCs isolated from the responders but not from the non-responders. Gene ontology analysis revealed that promoters with altered DNA methylation pattern were strongly enriched among genes belonging to immune pathways in responders, however no enrichments could be observed in the non-responders. Our findings suggest that BCG-induced epigenetic reprogramming of immune cell function can enhance anti-mycobacterial immunity in macrophages. Understanding why BCG induces this response in responders but not in nonresponders could provide clues to improvement of TB vaccine efficacy.

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NATURE PUBLISHING GROUP , 2017. Vol. 7, article id 12305
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Immunology in the medical area
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URN: urn:nbn:se:liu:diva-141932DOI: 10.1038/s41598-017-12110-2ISI: 000411677500009PubMedID: 28951586OAI: oai:DiVA.org:liu-141932DiVA, id: diva2:1149183
Note

Funding Agencies|Swedish Research Council [2012-3349, 2015-02593]; Swedish Heart Lung Foundation [20130685, 20150709]; Swedish Research Council; Knut and Alice Wallenberg Foundation

Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2018-03-28

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Verma, DeeptiRaffetseder, JohannaMartis, Mihaela-MariaBhai Mehta, RatneshLerm, Maria
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