Sensing of microbial viability orchestrates the metabolic recycling of engulfed bacteria in macrophages

Macrophages are professional phagocytes that can engulf and degrade multiple microbes at a time. This potentially creates a readily usable source of nutrients but how this can shape cellular metabolism and innate immune cell activation is poorly understood. Here, we show that phagocytosis of bacteria constitutes an alternative nutrient source, the use of which skew macrophage metabolism and is dictated by sensing of bacterial viability. Phagocytosis of killed bacteria maintains intracellular pool of adenosine monophosphate (AMP), stimulates AMP-activated protein kinase (AMPK) and inhibits mTORC1 but the engulfment of live bacteria transiently activates mTORC1, limits metabolic recycling of bacterial metabolites and blocks GSH biosynthesis. Overall design: RNA-seq of Wild type bone marrow-derived macrophages treated with Live E.coli/LPS/Dead E.coli/Dead E.coli + concanamycin