Stimulator of interferon genes (STING) expression in the enteric nervous system and contributions of glial STING in disease

BackgroundAppropriate host-microbe interactions are essential for enteric glial development and subsequent gastrointestinal function, but the potential mechanisms of microbe-glial communication are unclear. Here, we tested the hypothesis that enteric glia express the pattern recognition receptor stimulator of interferon genes (STING) and communicate with the microbiome through this pathway to modulate gastrointestinal inflammation. MethodsIn situ transcriptional labeling and immunohistochemistry were used to examine STING and IFN beta expression in enteric neurons and glia. Glial-STING KO mice (Sox10(CreERT2+/-);STING(fl/fl)) and IFN beta ELISA were used to characterize the role of enteric glia in canonical STING activation. The role of glial STING in gastrointestinal inflammation was assessed in the 3% DSS colitis model. ResultsEnteric glia and neurons express STING, but only enteric neurons express IFN beta. While both the myenteric and submucosal plexuses produce IFN beta with STING activation, enteric glial STING plays a minor role in its production and seems more involved in autophagy processes. Furthermore, deleting enteric glial STING does not affect weight loss, colitis severity, or neuronal cell proportions in the DSS colitis model. ConclusionTaken together, our data support canonical roles for STING and IFN beta signaling in the enteric nervous system through enteric neurons but that enteric glia do not use these same mechanisms. We propose that enteric glial STING may utilize alternative signaling mechanisms and/or is only active in particular disease conditions. Regardless, this study provides the first glimpse of STING signaling in the enteric nervous system and highlights a potential avenue of neuroglial-microbial communication.