Manganese enhances DNA-or RNA-mediated innate immune response by inducing phosphorylation of TANK-binding kinase 1

Trace metals are essential for various physiological processes, but their roles in innate immunity have not been fully explored. Here, we found that manganese (Mn) significantly enhanced DNA- mediated IFN-alpha, IFN-beta, and IFN-lambda 1 production. Microarray analysis demonstrated Mn highly upregulated 351 genes, which were involved in multiple biological functions related to innate immune response. Moreover, we found that Mn2+ alone activates phosphorylation of TANK- binding kinase 1 (TBK1). Inhibiting ataxia telangiectasia mutated (ATM) kinase using ATM inhibitor or siRNA suppressed Mn-enhanced DNA-mediated immune response with decreasing phosphorylation of TBK-1, suggesting that ATM involves in Mn-dependent phosphorylation of TBK1. Given that TBK1 is an essential medi-ator in DNA-or RNA-mediated signaling pathways, we further demonstrated that Mn2+ suppressed infection of HSV-1 (DNA virus) or Sendai virus (RNA virus) into human macrophages by enhancing antiviral immunity. Our finding highlights a beneficial role of Mn in nucleic-acid-based preventive or therapeutic reagents against infectious diseases.

Automated summary

Study found that manganese enhances DNA-mediated interferon production and boosts antiviral immunity, potentially offering a new approach for nucleic-acid-based treatment of infectious diseases.