Sensing between reactions - how the metabolic microenvironment shapes immunity

Perception of potential threat is key for survival. The immune system constantly patrols the organism scanning for potential pathogenic or malignant danger. Recent evidence suggests that immunosurveillance not only relies on classic receptors [e.g. Toll-like receptors (TLRs) or antibodies] but is also based on sensing of the metabolic environment. Metabolites interact in numerous ways with immune cells, and are therefore more than just reaction intermediates. This new perspective opens the door for potential, future therapeutic strategies. Here we describe how immune functionality during infections, cancer or autoimmunity, as exemplified by short-chain fatty acids, lactate and reactive oxygen species (ROS), can be shaped by metabolic intermediates.