Abstract：
:Bacillus Calmette-Guérin (BCG) is the only licensed vaccine for tuberculosis (TB) and induces highly variable protection against pulmonary disease in different countries. We hypothesised that DNA methylation is one of the molecular mechanisms driving variability in BCG-induced immune responses. DNA methylation in peripheral blood mononuclear cells (PBMC) from BCG vaccinated infants was measured and comparisons made between low and high BCG-specific cytokine responders. We found 318 genes and 67 pathways with distinct patterns of DNA methylation, including immune pathways, e.g. for T cell activation, that are known to directly affect immune responses. We also highlight signalling pathways that could indirectly affect the BCG-induced immune response: potassium and calcium channel, muscarinic acetylcholine receptor, G Protein coupled receptor (GPCR), glutamate signalling and WNT pathways. This study suggests that in addition to immune pathways, cellular processes drive vaccine-induced immune responses. Our results highlight mechanisms that require consideration when designing new TB vaccines.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Hasso-Agopsowicz M,Scriba TJ,Hanekom WA,Dockrell HM,Smith SGdoi
10.1038/s41598-018-31537-9subject
Has Abstractpub_date
2018-08-30 00:00:00pages
13086issue
1issn
2045-2322pii
10.1038/s41598-018-31537-9journal_volume
8pub_type
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