Glycolytic side pathways regulating macrophage inflammatory phenotypes and functions

Macrophages are crucial effector cells of the innate immune system and have important roles in the initiation and resolution of inflammation as well as in tissue homeostasis. To fulfill these diverse roles, macrophages exhibit metabolic flexibility to quickly adapt to the needs of the effector functions required, as well as to the microenvironment. This metabolic flexibility is exemplified by proinflammatory macrophages, which upregulate glycolysis to both initiate and sustain the process of inflammation. Upregulation of glycolysis does not only represent a fast means of ATP generation. It also fuels glycolytic side pathways that are crucial for an effective inflammatory response by influencing the cell's redox balance as well as by providing building blocks and substrates for epigenetic reprogramming. The aim of this short review is to explore how three of these pathways - the pentose phosphate pathway, the glycerol phosphate shuttle, and the serine synthesis pathway - help macrophages sustain their proinflammatory phenotype and functions.