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

Hongyan Sui1, Qian Chen1, Jun Yang1

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

Iscience
|November 3, 2022
PubMed

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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