Rewiring cellular metabolism via the AKT/mTOR pathway contributes to host defence against Mycobacterium tuberculosis in human and murine cells (original) (raw)

Cells in homeostasis metabolise glucose mainly through the tri-carboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS), whilst activated cells switch their basal metabolism to aerobic glycolysis. In thus study, we examined whether metabolic reprogramming towards aerobic glycolysis is important for the host response to Mycobacterium tuberculosis (Mtb). Through transcriptional and metabolite analysis we show that Mtb induces a switch in host cellular metabolism towards aerobic glycolysis in human peripheral blood mononuclear cells (PBMCs). The metabolic switch is TLR2-dependent but NOD2-independent, and is mediated in part through activation of the AKT-mTOR pathway. We show that pharmacological inhibition of the AKT/mTOR pathway inhibits cellular responses to Mtb both in vitro in human peripheral blood mononuclear cells, and in vivo in a model of murine tuberculosis. Our findings reveal a novel regulatory layer of host responses to Mtb which will aid understanding of host s...