Binding of bacterial secondary messenger molecule c di-GMP is a STING operation

Initial skirmishes between the host and pathogen result in spillage of the contents of the bacterial cell.Amongst the spillage,the secondary messenger molecule,cyclic dimeric guanosine monophosphate(c di-GMP),was recently shown to be bound by stimulator of interferon genes(STING).Binding of c di-GMP by STING activates the Tank Binding Kinase(TBK1)mediated signaling cascades that galvanize the body’s defenses for elimi-nation of the pathogen.In addition to c di-GMP,STING has also been shown to function in innate immune re-sponses against pathogen associated molecular pat-terns(PAMPs)originating from the DNA or RNA of pathogens.The pivotal role of STING in host defense is exemplified by the fact that STING-/-mice die upon infection by HSV-1.Thus,STING plays an essential role in innate immune responses against pathogens.This opens up an exciting possibility of targeting STING for development of adjuvant therapies to boost the im-mune defenses against invading microbes.Similarly,STING could be targeted for mitigating the inflamma-tory responses augmented by the innate immune sys-tem.This review summarizes and updates our current understanding of the role of STING in innate immune responses and discusses the future challenges in de-lineating the mechanism of STING-mediated responses.