Itaconate: the poster child of metabolic reprogramming in macrophage function

Abstract

Itaconate is one of the best examples of the consequences of metabolic reprogramming during immunity. It is made by diverting aconitate away from the tricarboxylic acid cycle during inflammatory macrophage activation. The main reason macrophages exhibit this response currently appears to be for an anti-inflammatory effect, with itaconate connecting cell metabolism, oxidative and electrophilic stress responses and immune responses. A role for itaconate in the regulation of type I interferons during viral infection has also been described, as well as in M2 macrophage function under defined circumstances. Finally, macrophage-specific itaconate production has also been shown to have a pro-tumour effect. All of these studies point towards itaconate being a critical immunometabolite that could have far-reaching consequences for immunity, host defence and tumorigenesis.