Immunity 48, 675–678 (2018)

Manganese (Mn) regulates the function of various types of enzymes. In Immunity, Jiang and colleagues show that Mn2+ is required for the induction of interferon responses to DNA viruses. Viral infection induces the cytoplasmic release of Mn from the Golgi and mitochondria. Mn2+ increases the enzymatic activity of the DNA sensor cGAS and its sensitivity to double-stranded DNA, as well as the affinity with which the signaling intermediate cGAMP binds to the downstream adaptor STING. Mice on a Mn-deficient diet are highly susceptible to infection with sub-lethal doses of the viruses HSV and VACV, with alveolar and peritoneal macrophages from these mice showing diminished type 1 interferon responses to DNA viruses but not to RNA viruses.