Metabolic needs of brain-infiltrating leukocytes and microglia in multiple sclerosis

Metabolism, the umbrella term for complex biochemical pathways that sustain the basic functions of life, has garnered attention in recent years for its role in immune activation. Indeed, metabolic pathways and their intricate and complex connections with immune mechanisms constitute a new area of immunology termed 'immunometabolism'. One highlight is the existence of a switch in the key metabolic programs in immune cells, which executes their effector functions. 'Metabolic reprogramming' is observed in conditions of both peripheral diseases as well as in neurodegenerative conditions associated with inflammation such as multiple sclerosis. Moreover metabolic reprogramming occurs for almost every immune cell type. Whether metabolic changes are cause or effect of immune activation, however, remains to be fully understood. Being central to cellular activation, metabolism has become very topical in terms of exploring therapeutic targets. This review covers the major metabolic programs in immune cells, discuss metabolites as regulators of immune cell functions, and consider metabolic enzymes or pathways as therapeutic targets using examples from multiple sclerosis and its animal models.