Molecular and spatial mechanisms governing STING signalling

Detection of microbial nucleic acids via innate immune receptors is critical for establishing host defence against pathogens. The DNA‐sensing cGAS‐STING pathway has gained increasing attention in the last decade as a key pathway for combating viral and bacterial infections. cGAS‐STING activation primarily promotes the secretion of antiviral type I IFNs via the key transcription factor, IRF3. In addition, cGAS‐STING signalling also elicits proinflammatory cytokines through NF‐κB activity. Activation of IRF3 and NF‐κB is mediated by the chief signalling receptor protein STING. Interestingly, STING undergoes significant trafficking events across multiple subcellular locations, which regulates both the activation of downstream signalling pathways, as well as appropriate termination of the responses. Studies to date have provided a comprehensive view of the regulation and role of the IRF3‐IFN pathway downstream of STING. However, many aspects of STING signalling remain relatively poorly defined. This review will explore the current understanding of the mechanisms through which STING elicits inflammatory and antimicrobial responses, focusing on the precise signalling and intracellular trafficking events that occur. We will also discuss exciting and emerging concepts in the field, including the importance of IFN‐independent STING responses for host defence and during STING‐related disease.

• Publication year

  2020

• Venue

  The FEBS Journal

• Publication date

  2020-11-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/febs.15640PMID 33237620
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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