The interactions between cGAS-STING pathway and pathogens

Abstract

Cytosolic DNA is an indicator of pathogen invasion or DNA damage. The cytosolic DNA sensor cyclic guanosine monophosphateadenosine monophosphate (cGAMP) synthase (cGAS) detects DNA and then mediates downstream immune responses through the molecule stimulator of interferon genes (STING, also known as MITA, MPYS, ERIS and TMEM173). Recent studies focusing on the roles of the cGAS-STING pathway in evolutionary distant species have partly sketched how the mammalian cGAS-STING pathways are shaped and have revealed its evolutionarily conserved mechanism in combating pathogens. Both this pathway and pathogens have developed sophisticated strategies to counteract each other for their survival. Here, we summarise current knowledge on the interactions between the cGAS-STING pathway and pathogens from both evolutionary and mechanistic perspectives. Deeper insight into these interactions might enable us to clarify the pathogenesis of certain infectious diseases and better harness the cGAS-STING pathway for antimicrobial methods.

Innate Immune DNA Sensing of Flaviviruses

“…It is also the host DNA sensing pathway that has been shown to be most implicated during flaviviruses replication and studied in that context. This innate immune sensory system surveys the host cytosolic space for double-stranded DNA and RNA/DNA hybrids regardless of the specific sequence, whose presence usually indicates a pathogen infection or DNA damage inside the nucleus [37,[68][69][70]. Activated cGAS produces secondary messenger 2 3 -cGAMP through dimerization that can diffuse across neighboring cells and bind and activate downstream adaptor STING [71,72].…”

Cytosolic DNA‐STING‐NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide

“…Stimulator of interferon gene (STING) (also known as MITA, TMEM173, ERIS, and MPYS), acting as a crucial regulator of the DNA sensing pathway, is physiologically embedded in endoplasmic reticulum and could evoke the production of type I interferon by activating nuclear factor-Κb, as well as interferons regulatory factor 3 pathways. [9][10][11] In innate immunity, STING is activated by cyclic guanosine monophosphate (GMP)adenosine monophosphate (AMP) (cGAMP) synthase (cGAS), which participates in multiple pathological and physiological processes, involving host defense against microbial infections, 12 cellular senescence, 13 antitumor immunity, 14 autoimmunity, 15 autophagy, as well as many inflammatory diseases. 16 For instance, in human myeloid cells, targeting the cGAS-STING-NLRP3 axis could mitigate inflammasome response during bacterial and viral infections.…”

Generation of a Novel Mesothelin-Targeted Oncolytic Herpes Virus and Implemented Strategies for Manufacturing

“…The nucleic acid sensing pathway based on STING protein is involved in recognition of different species of both DNA and RNA viruses [ 69 ]. Accordingly, many viral species have developed molecular mechanisms to inhibit STING axis at different levels of the pathway cascade, to evade interferons-mediated viral clearance [ 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ].…”