Manganese enhances DNA- or RNA-mediated innate immune response by inducing phosphorylation of TANK-binding kinase 1
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Updated: Aug 23, 2025

Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
Hongyan Sui1, Qian Chen1, Jun Yang1
1Laboratory 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.
Insights
Manganese (Mn) boosts innate immunity by enhancing DNA-mediated interferon production and activating key signaling proteins. This trace metal also improves antiviral defense against DNA and RNA viruses.
Area of Science:
- Immunology
- Trace Metal Biology
- Virology
Background:
- Trace metals are vital for physiological functions.
- The role of manganese (Mn) in innate immunity requires further investigation.
- Interferons (IFNs) are crucial for antiviral defense.
Purpose of the Study:
- To explore the role of manganese in innate immunity.
- To investigate the molecular mechanisms underlying Mn-mediated immune enhancement.
- To assess the potential of Mn in antiviral strategies.
Main Methods:
- Stimulation of immune cells with manganese (Mn).
- Measurement of interferon production (IFN-α, IFN-β, IFN-λ1).
- Gene expression analysis using microarrays.
- Western blotting to detect protein phosphorylation (TBK1, ATM).
- Viral challenge assays (HSV-1, Sendai virus) in human macrophages.
Main Results:
- Manganese significantly enhanced DNA-mediated IFN-α, IFN-β, and IFN-λ1 production.
- Mn upregulated 351 genes involved in innate immune responses.
- Mn2+ activated TANK-binding kinase 1 (TBK1) phosphorylation, dependent on ATM kinase.
- Mn2+ suppressed HSV-1 and Sendai virus infections in human macrophages by enhancing antiviral immunity.
Conclusions:
- Manganese plays a beneficial role in innate immunity, particularly in nucleic acid-mediated responses.
- The ATM-TBK1 signaling pathway is involved in Mn-dependent immune activation.
- Manganese shows potential as a therapeutic agent against viral infections.
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