Negative Regulation of Cytosolic Sensing of DNA

Int Rev Cell Mol Biol. 2019:344:91-115. doi: 10.1016/bs.ircmb.2018.09.002. Epub 2018 Oct 29.

Abstract

In mammals, cytosolic detection of nucleic acids is critical in initiating innate antiviral responses against invading pathogens (like bacteria, viruses, fungi and parasites). These programs are mediated by multiple cytosolic and endosomal sensors and adaptor molecules (c-GAS/STING axis and TLR9/MyD88 axis, respectively) and lead to the production of type I interferons (IFNs), pro-inflammatory cytokines, and chemokines. While the identity and role of multiple pattern recognition receptors (PRRs) have been elucidated, such immune surveillance systems must be tightly regulated to limit collateral damage and prevent aberrant responses to self- and non-self-nucleic acids. In this review, we discuss recent advances in our understanding of how cytosolic sensing of DNA is controlled during inflammatory immune responses.

Keywords: Auto-inflammation; Infertility; Inflammasome; Interferon; NLRP14; Nucleic acid sensing; Post-translational modifications; RIG-I; STING; TBK1; cGAS.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cytosol / metabolism*
  • DNA / metabolism*
  • Humans
  • Immunity, Innate
  • Inflammation / pathology
  • NLR Proteins / metabolism
  • Signal Transduction

Substances

  • NLR Proteins
  • DNA