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Review
. 2019 Dec 11;51(12):1-10.
doi: 10.1038/s12276-019-0333-0.

STING signaling and host defense against microbial infection

Jeonghyun Ahn  1 , Glen N Barber  2
Affiliations
Review

STING signaling and host defense against microbial infection

Jeonghyun Ahn et al. Exp Mol Med. .

Abstract

The first line of host defense against infectious agents involves activation of innate immune signaling pathways that recognize specific pathogen-associated molecular patterns (PAMPs). Key triggers of innate immune signaling are now known to include microbial-specific nucleic acid, which is rapidly detected in the cytosol of the cell. For example, RIG-I-like receptors (RLRs) have evolved to detect viral RNA species and to activate the production of host defense molecules and cytokines that stimulate adaptive immune responses. In addition, host defense countermeasures, including the production of type I interferons (IFNs), can also be triggered by microbial DNA from bacteria, viruses and perhaps parasites and are regulated by the cytosolic sensor, stimulator of interferon genes (STING). STING-dependent signaling is initiated by cyclic dinucleotides (CDNs) generated by intracellular bacteria following infection. CDNs can also be synthesized by a cellular synthase, cGAS, following interaction with invasive cytosolic self-DNA or microbial DNA species. The importance of STING signaling in host defense is evident since numerous pathogens have developed strategies to prevent STING function. Here, we review the relevance of STING-controlled innate immune signaling in host defense against pathogen invasion, including microbial endeavors to subvert this critical process.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Activation of STING signaling and viral evasion.
STING is activated by cyclic dinucleotides (CDNs) secreted by intracellular bacteria or non-canonical CDNs generated by cGAS. The sensing and interaction of CDNs influences a conformational change in STING and triggers the trafficking of STING complexed with TBK1 from the ER to endosomal/lysosomal perinuclear regions. Translocated TBK1 leads to the phosphorylation of IRF3 and NF-kB to induce type I IFNs or inflammatory cytokines. Microbial DNA or RNA interacts with cGAS/STING to evade critical innate immune signaling. Red letters: DNA virus proteins, blue letters: RNA virus proteins
See this image and copyright information in PMC

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