Lachmandas E, et al. - Considering the proposal of metformin as a candidate adjunctive host-directed therapy for tuberculosis, researchers investigated its effects on human host responses to Mycobacterium tuberculosis. They examined in-vitro and in-vivo effects of metformin in humans. Addition of metformin to peripheral blood mononuclear cells from healthy volunteers intensified in-vitro cellular metabolism whilst inhibiting the mammalian target of rapamycin (mTOR) targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation, and increased phagocytosis. Healthy human volunteers on receiving metformin showed significant down-regulation of genes involved in oxidative phosphorylation, mTOR signaling and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and increased upregulation of genes involved in phagocytosis and reactive oxygen species (ROS) production. These observations suggest a range of potentially beneficial effects of metformin on cellular metabolism, immune function and gene-transcription involved in innate host responses to M. tuberculosis.