TCA metabolism regulates DNA hypermethylation in LPS and <i>Mycobacterium tuberculosis</i>-induced immune tolerance.

ABSTRACT: Severe and chronic infections, including pneumonia, sepsis, and tuberculosis (TB), induce long-lasting epigenetic changes that are associated with an increase in all-cause postinfectious morbidity and mortality. Oncology studies identified metabolic drivers of the epigenetic landscape, with the tricarboxylic acid (TCA) cycle acting as a central hub. It is unknown if the TCA cycle also regulates epigenetics, specifically DNA methylation, after infection-induced immune tolerance. The following studies demonstrate that lipopolysaccharide and Mycobacterium tuberculosis induce changes in DNA methylation that are mediated by the TCA cycle. Infection-induced DNA hypermethylation is mitigated by inhibitors of cellular metabolism (rapamycin, everolimus, metformin) and the TCA cycle (isocitra

SUBMITTER: Abhimanyu 

PROVIDER: S-EPMC11474056 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature