The Cytosolic Sensor STING is Required for Intestinal Homeostasis and Control of Inflammation

STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.