Differential DNA methylation of potassium channel KCa3.1 and immune signalling pathways is associated with infant immune responses following BCG vaccination

Scientific Reports
Mateusz Hasso-AgopsowiczSteven G Smith

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.

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Citations

Apr 21, 2020·The Cochrane Database of Systematic Reviews·Carlo Di PietrantonjVittorio Demicheli

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Methods Mentioned

BETA
FACS
PMA
density gradient centrifugation
Assay

Software Mentioned

Bismark Methylation Extractor
FastQC
SeqMonk
Rstudio
TrimGalore
Panther Pathway Analysis and Cytospace
Bismark
StataSE
Bowtie2
Cutadapt

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