Itaconate drives mtRNA-mediated type I interferon production through inhibition of succinate dehydrogenase.

Itaconate is one of the most highly upregulated metabolites in inflammatory macrophages and has been shown to have immunomodulatory properties. Here, we show that itaconate promotes type I interferon production through inhibition of succinate dehydrogenase (SDH). Using pharmacological and genetic approaches, we show that SDH inhibition by endogenous or exogenous itaconate leads to double-stranded mitochondrial RNA (mtRNA) release, which is dependent on the mitochondrial pore formed by VDAC1.

Itaconate boosts malaria via induction of PD-L1.

The Krebs-cycle-derived metabolite itaconate has been shown to be immunomodulatory, targeting multiple processes in macrophages. Ramalho et al. reveal an additional role for itaconate in malaria.