Cyclic Dinucleotides in the Scope of the Mammalian Immune System

Handb Exp Pharmacol. 2017:238:269-289. doi: 10.1007/164_2016_5002.

Abstract

First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system. In this regard, our main focus is the role of the cGAS-STING axis in the context of microbial infection and sterile inflammation and its implications for therapeutic applications.

Keywords: Cyclic dinucleotides; Innate immunity; STING; cGAMP; cGAS.

Publication types

  • Review

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Bacterial Infections / drug therapy
  • Bacterial Infections / immunology
  • Bacterial Infections / microbiology*
  • Cyclic AMP / chemistry
  • Cyclic AMP / immunology
  • Cyclic AMP / metabolism*
  • Cyclic AMP / therapeutic use
  • Cyclic GMP / chemistry
  • Cyclic GMP / immunology
  • Cyclic GMP / metabolism*
  • Cyclic GMP / therapeutic use
  • Evolution, Molecular
  • Humans
  • Immune System / drug effects
  • Immune System / immunology
  • Immune System / metabolism*
  • Immune System / microbiology
  • Immunity, Innate
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Molecular Structure
  • Second Messenger Systems* / drug effects

Substances

  • Adjuvants, Immunologic
  • Membrane Proteins
  • STING1 protein, human
  • Cyclic AMP
  • Cyclic GMP