Time and Demand are Two Critical Dimensions of Immunometabolism: The Process of Macrophage Activation and the Pentose Phosphate Pathway.

A process is a function of time; in immunometabolism, this is reflected by the stepwise adaptation of metabolism to sustain the bio-energetic demand of an immune-response in its various states and shades. This perspective article starts by presenting an early attempt to investigate the physiology of inflammation, in order to illustrate one of the basic concepts of immunometabolism, wherein an adapted metabolism of infiltrating immune cells affects tissue function and inflammation. We then focus on the process of macrophage activation and aim to delineate the factor time within the current molecular context of metabolic-rewiring important for adapting primary carbohydrate metabolism. In the last section, we will provide information on how the pentose phosphate pathway may be of importance to provide both nucleotide precursors and redox-equivalents, and speculate how carbon-scrambling events in the non-oxidative pentose phosphate pathway might be regulated within cells by demand. We conclude that the adapted metabolism of inflammation is specific in respect to the effector-function and appears as a well-orchestrated event, dynamic by nature, and based on a functional interplay of signaling- and metabolic-pathways.