DNA sensor cGAS-mediated immune recognition

Protein Cell. 2016 Nov;7(11):777-791. doi: 10.1007/s13238-016-0320-3. Epub 2016 Sep 30.

Abstract

The host takes use of pattern recognition receptors (PRRs) to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFκB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types. cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon production. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs.

Keywords: DNA sensors; cGAMP; cGAS; cytosolic DNAs; innate immunity.

Publication types

  • Review

MeSH terms

  • DNA, Bacterial / immunology*
  • DNA, Bacterial / metabolism
  • DNA, Viral / immunology*
  • DNA, Viral / metabolism
  • Gene Expression Regulation
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate*
  • Interferon Regulatory Factor-3 / genetics
  • Interferon Regulatory Factor-3 / immunology*
  • Interferon Type I / biosynthesis
  • Interferon Type I / immunology
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Models, Molecular
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Nucleotides, Cyclic / biosynthesis
  • Nucleotides, Cyclic / immunology
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / immunology*
  • Protein Binding
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / immunology
  • Signal Transduction

Substances

  • DNA, Bacterial
  • DNA, Viral
  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Interferon Type I
  • Membrane Proteins
  • NF-kappa B
  • Nucleotides, Cyclic
  • STING protein, human
  • cyclic guanosine monophosphate-adenosine monophosphate
  • Protein-Serine-Threonine Kinases
  • TBK1 protein, human
  • MB21D1 protein, human
  • Nucleotidyltransferases