TCA metabolism regulates DNA hypermethylation in LPS and Mycobacterium tuberculosis–induced immune tolerance

Severe and chronic infections, including pneumonia, sepsis, and tuberculosis (TB), induce long-lasting epigenetic changes that are associated with an increase in all cause post-infectious morbidity and mortality. We show that TCA cycle also regulates epigenetics, specifically DNA methylation, after infection induced immune tolerance. The following data is DNA methylation from lipopolysaccharide (LPS) in presence of by inhibitors of cellular metabolism (rapamycin, everolimus, metformin) and the TCA cycle (IDH inhibitors). DNA methylation profiles were also generated from exogenous supplementation with TCA metabolites (succinate and itaconate) in Monocyte derived Macrophages Bisulphite converted DNA from the four sample across 6 conditions; 23samples and 6 samples from metabolite treated cells total 29 samples were hybridised to the Illumina EPIC 850K