title: Binding of bacterial secondary messenger molecule c di-GMP is a STING operation.
abstract: 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 elimination of the pathogen. In addition to c di-GMP, STING has also been shown to function in innate immune responses against pathogen associated molecular patterns (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 immune defenses against invading microbes. Similarly, STING could be targeted for mitigating the inflammatory responses augmented by the innate immune system. This review summarizes and updates our current understanding of the role of STING in innate immune responses and discusses the future challenges in delineating the mechanism of STING-mediated responses.
authors.affiliation: Tianjin Key Laboratory of Protein Science, School of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Neil
authors.initials: N
authors.lastname: Shaw
authors.forename: Songying
authors.initials: S
authors.lastname: Ouyang
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D019281:Dimerization; D006561:Herpes Simplex / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012367:RNA, Viral / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015290:Second Messenger Systems
chemical_list: D008565:Membrane Proteins; D012367:RNA, Viral; D050800:STAT6 Transcription Factor; D006152:Cyclic GMP