摘要： Macrophages are activated during microbial infection to coordinate inflammatory responses and host defense. However, how such inflammatory responses are regulated commensurate with the degree of microbial infection is not well understood. Here we show that in macrophages activated by bacterial lipopolysaccharide (LPS), mitochondrial glycerol 3-phosphate dehydrogenase (GPD2) regulates glucose oxidation to drive inflammatory responses. GPD2, a component of the glycerol phosphate shuttle (GPS), boosts glucose oxidation to fuel Acetyl-CoA production, histone acetylation and inflammatory gene induction. While acute LPS exposure drives macrophage activation, prolonged exposure triggers entry into LPS tolerance, where macrophages orchestrate immunosuppression to limit the detrimental effects of sustained inflammation. We find that the shift in the inflammatory response is modulated by GPD2, which coordinates a shutdown of oxidative metabolism that limits Acetyl-CoA availability  for histone acetylation at inflammatory genes, thus contributing to suppression of inflammatory responses. Therefore, GPD2 and the GPS integrate the extent of microbial stimulation with glucose oxidation to balance the beneficial and detrimental effects of the inflammatory response.