Manganese Enhances DNA- or RNA-Mediated Innate Immune Response by Inducing Phosphorylation of TANK-Binding Kinase 1

Transition metals are essential for various physiological processes, but their roles in innate immunity have not been fully explored. Here, we found that among seven tested metal ions, only manganese (Mn) significantly enhanced DNA-mediated IFN-α, IFN-β, and IFN-λ1 production. Microarray analysis demonstrated that 351 genes were highly upregulated by Mn2+, and those genes were involved in multiple biological processes related to innate immune response. Moreover, we discovered that Mn2+ alone activates phosphorylation of TANK-binding kinase 1 (TBK1). Given that TBK1 is an essential mediator in many DNA- or RNA-mediated signaling pathways, we further demonstrated that Mn2+ suppressed infection with HSV-1 (a DNA virus) and Sendai virus (an RNA virus) in human macrophages by enhancing virus infection-triggered antiviral immunity. Our finding highlights the beneficial role of manganese in nucleic-acid-based preventive or therapeutic reagents against infectious diseases. The finding may add value for the development of strategies against the current COVID-19 pandemic.