Methylglyoxal activates the NRF2 pathway and impairs immune responses controlling the growth control of Mycobacterium tuberculosis (Mtb) in macrophages.

We compared the transcriptome profile of M. tuberculosis-infected murine bone marrow derived macrophages (BMM) treated or not with 200 uM methylglyoxal (MGO) and uninfected controls as described below. We found 3606 differentially expressed genes (DEGs) between uninfected and M. tuberculosis-infected BMM, being approximately half of these upregulated . 1699 DEGs were determined by comparing Mtb-MGO vs M. tuberculosis BMM, with 2/3 of these DEGs downregulated. Genes in the glyoxalate, glutathione and selenocompound metabolic KEEG pathways were increased comparing Mtb-MGO vs M. tuberculosis BMM. Instead genes involved in type I IFN responses, cytokine receptor and chemokine signalling gene ontology clusters (GO) were increased after infection with Mtb as compared to uninfected controls and decreased in Mtb-MGO vs M. tuberculosis BMM. Overall design: RNA seq was performed in triplicate independent cultures of BMM treated or not with 200 uM MGO, infected 4 h after treatment with M. tuberculosis at a MOI of 5:1. RNA was extracted 4h after Mtb infection from uninfected BMM controls (Control), Mtb infected BMM (Mtb), and MGO-treated, Mtb-infected BMM (Mtb-MGO).