The role of the cGAS-STING signaling pathway in viral infections, inflammatory and autoimmune diseases

Acta Pharmacol Sin. 2024 Oct;45(10):1997-2010. doi: 10.1038/s41401-023-01185-5. Epub 2024 Jun 1.

Abstract

Pattern recognition receptors are an essential part of the immune system, which detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and help shape both innate and adaptive immune responses. When dsDNA is present, cyclic GMP-AMP Synthase (cGAS) produces a second messenger called cyclic GMP-AMP (cGAMP), which then triggers an adaptor protein called STING, and eventually activates the expression of type I interferon (IFN) and pro-inflammatory cytokines in immune cells. The cGAS-STING signaling pathway has been receiving a lot of attention lately as a key immune-surveillance mediator. In this review, we summarize the present circumstances of the cGAS-STING signaling pathway in viral infections and inflammatory diseases, as well as autoimmune diseases. Modulation of the cGAS-STING signaling pathway provides potential strategies for treating viral infections, inflammatory diseases, and autoimmune diseases.

Keywords: autoimmune diseases; cGAS-STING signaling pathway; double-stranded DNA (dsDNA); inflammatory diseases; type I interferon (IFN); viral infections.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases* / immunology
  • Autoimmune Diseases* / metabolism
  • Humans
  • Inflammation* / immunology
  • Inflammation* / metabolism
  • Membrane Proteins* / metabolism
  • Nucleotidyltransferases* / metabolism
  • Signal Transduction*
  • Virus Diseases* / immunology
  • Virus Diseases* / metabolism

Substances

  • Nucleotidyltransferases
  • STING1 protein, human
  • cGAS protein, human
  • Membrane Proteins