actively suppresses innate immune nucleic acid receptors.

Chronic mucosal pathogens have evolved multiple strategies to manipulate the host immune response; consequently, microbes contribute to the development of >2 million cases of cancer/year. Gastric adenocarcinoma is the fourth leading cause of cancer-related death and confers the highest risk for this disease. Gastric innate immune effectors can either eliminate bacteria or mobilize adaptive immune responses including Toll-like receptors (TLRs), and cytosolic DNA sensor/adaptor proteins (e.g., stimulator of interferon genes, STING). The strain-specific type IV secretion system (T4SS) augments gastric cancer risk and translocates DNA into epithelial cells where it activates the microbial DNA sensor TLR9 and suppresses injury ; however, the ability of to suppress additional nucleic acid PRRs within the context of chronic gastric inflammation and injury remains undefined. In this study, and experiments identified a novel mechanism through which actively suppresses STING and RIG-I signaling via downregulation of IRF3 activation. , the use of genetically deficient mice revealed that Th17 inflammatory responses are heightened following infection within the context of deficiency in conjunction with increased expression of a known host immune regulator, Trim30a. This novel mechanism of immune suppression by is likely a critical component of a finely tuned rheostat that not only regulates the initial innate immune response, but also drives chronic gastric inflammation and injury.