Methionine modulates the metabolic-epigenetic axis as an immunotherapeutic in tuberculosis-isotopomer dataset
Description
The methionine metabolism is central to epigenetic reprogramming to produce pro29 inflammatory cytokines. Disruptions in methionine metabolism contribute to complex disorders, providing an important target for nutrient interventions. Here, Mycobacterium tuberculosis (Mtb) H37Rv-infected C57BL/6 mice showed functional heterogeneity between alveolar and non-alveolar macrophage (AMs/Non-AMs) with major metabolic reprogramming in Non-AMs. Global metabolite and proteome analysis of Mtb-infected bone marrow-derived macrophages (BMDMs) showed a diversion of flux from methionine metabolism towards increased nucleotide salvage and glutathione (GSH) production. Carbon units of 13C5- methionine via isotopomer analysis contributed to polyamine synthesis, fuelling the nucleotide salvage node in Mtb-infected BMDMs. Methionine supplementation increased mycobacterial clearance in C57BL/6 mice and in BMDMs by promoting a pro-inflammatory response, as evident by increased IL-1β and IFN-γ. Increased IL-1β production is mainly contributed to by increased H3K4 trimethylation in macrophages. These findings reveal an important strategy by which methionine supplementation in macrophages and mice remodels host metabolism to enhance acute pro-inflammatory responses and exploit dietary supplementation to improve nutritional immunity in TB. This dataset contains metabolomics data for Mtb-infected and control BMDMs cultured with 13C5-Methionine (Isotopomer.rar) and experimental design (Sampledetails_Isotopomer.csv).
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Institutions
- International Centre for Genetic Engineering and BiotechnologyDelhi, New Delhi