Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses. Academic Article uri icon

Overview

abstract

  • Manganese (Mn) is essential for many physiological processes, but its functions in innate immunity remain undefined. Here, we found that Mn2+ was required for the host defense against DNA viruses by increasing the sensitivity of the DNA sensor cGAS and its downstream adaptor protein STING. Mn2+ was released from membrane-enclosed organelles upon viral infection and accumulated in the cytosol where it bound directly to cGAS. Mn2+ enhanced the sensitivity of cGAS to double-stranded DNA (dsDNA) and its enzymatic activity, enabling cGAS to produce secondary messenger cGAMP in the presence of low concentrations of dsDNA that would otherwise be non-stimulatory. Mn2+ also enhanced STING activity by augmenting cGAMP-STING binding affinity. Mn-deficient mice showed diminished cytokine production and were more vulnerable to DNA viruses, and Mn-deficient STING-deficient mice showed no increased susceptibility. These findings indicate that Mn is critically involved and required for the host defense against DNA viruses.

publication date

  • April 10, 2018

Research

keywords

  • DNA Virus Infections
  • DNA Viruses
  • DNA, Viral
  • Manganese
  • Membrane Proteins
  • Nucleotidyltransferases

Identity

Scopus Document Identifier

  • 85045006462

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2018.03.017

PubMed ID

  • 29653696

Additional Document Info

volume

  • 48

issue

  • 4