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

doi:10.1016/j.isci.2022.105352

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

iScience. 2022 Oct 13;25(11):105352. doi: 10.1016/j.isci.2022.105352. eCollection 2022 Nov 18.

Authors

Hongyan Sui¹, Qian Chen¹, Jun Yang¹, Selena Srirattanapirom¹, Tomozumi Imamichi¹

Affiliation

¹ Laboratory of Human Retrovirology and Immunoinformatics, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

Abstract

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.

Keywords: Biochemistry; Immunology; Molecular physiology.