iScience (Nov 2022)

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

  • Hongyan Sui,
  • Qian Chen,
  • Jun Yang,
  • Selena Srirattanapirom,
  • Tomozumi Imamichi

Journal volume & issue
Vol. 25, no. 11
p. 105352

Abstract

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Summary: 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-α, IFN-β, and IFN-λ1 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 mediator 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.

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