DNA PAMPs as Molecular Tools for the cGAS-STING Signaling Pathways

Methods Mol Biol. 2025:2854:117-125. doi: 10.1007/978-1-0716-4108-8_13.

Abstract

Beyond its role as the bearer of genetic material, DNA also plays a crucial role in the activation phase of innate immunity. Pathogen recognition receptors (PRRs) and their homologs, pathogen-associated molecular patterns (PAMPs), form the foundation for driving innate immune activation and the induction of immune responses during infection. In the context of DNA viruses or bacterial infections, specific DNA sequences are recognized and bound by DNA sensors, marking the DNA as a PAMP for host recognition and subsequent activation of innate immunity. The primary DNA sensor pathway known to date is cGAS-STING, which can induce Type I interferons (IFN) and innate immune responses against viruses and bacteria. Additionally, the cGAS-STING pathway has been identified to mediate functions in autophagy and senescence. Herein, we introduce methods for using DNA PAMPs as molecular tools to study the role of cGAS-STING and its signaling pathway in regulating innate immunity, both in vitro and in vivo.

Keywords: DNA PAMPs; Innate immunity; cGAS-STING; dsDNA.

MeSH terms

  • Animals
  • DNA* / genetics
  • DNA* / metabolism
  • Humans
  • Immunity, Innate*
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice
  • Nucleotidyltransferases* / genetics
  • Nucleotidyltransferases* / metabolism
  • Pathogen-Associated Molecular Pattern Molecules / immunology
  • Pathogen-Associated Molecular Pattern Molecules / metabolism
  • Signal Transduction*

Substances

  • Nucleotidyltransferases
  • Membrane Proteins
  • DNA
  • Pathogen-Associated Molecular Pattern Molecules
  • STING1 protein, human
  • cGAS protein, human