固有免疫信号分子STING研究进展
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摘要
干扰素基因刺激分子(stimulator of interferon genes,STING)是调控I型干扰素基因表达的重要信号分子之一,在抗感染固有免疫应答中具有重要的作用。研究发现STING参与病毒或细菌dsDNA或RNA刺激引起的固有免疫信号转导途径,STING作为信号转导接头蛋白能募集TBK1并激活IRF-3(interferon regulatory factor 3,干扰素调节因3)诱导1型IFN的产生,进而调控抗感染固有免疫应答反应。本文就目前STING的研究进展作一综述。
As a key signaling molecule in regulating the expression of type 1 interferon,STING(stimulator of interferon genes) play an important role in anti-infection innate immunity.It’s reported that STING participates in virus-or bacteria-derived dsDNA or RNA stimulated innate immunity signaling pathway by recruiting TBK1 and activating IRF3 to induce the production of type 1 interferon.This paper summarizes the recent advancement in exploring the biological function of STING.
As a key signaling molecule in regulating the expression of type 1 interferon,STING(stimulator of interferon genes) play an important role in anti-infection innate immunity.It’s reported that STING participates in virus-or bacteria-derived dsDNA or RNA stimulated innate immunity signaling pathway by recruiting TBK1 and activating IRF3 to induce the production of type 1 interferon.This paper summarizes the recent advancement in exploring the biological function of STING.
引文
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[2]Nagata S,Hanayama R,Kawane K.Autoimmunity and theclearance of dead cells[J].Cell,2010,140(5):619-630.
[3]Kawai T,Akira S.The roles of TLRs,RLRs and NLRs inpathogen recognition[J].Int Immunol,2009,21(4):317-337.
[4]Ishikawa H,Ma Z,Barber GN.STING regulatesintracellular DNA-mediated,type I interferon-dependentinnate immunity[J].Nature,2009,461(7265):788-792.
[5]Ishikawa H,Barber GN.STING is an endoplasmicreticulum adaptor that facilitates innate immunesignalling[J].Nature,2008,455(7213):674-678.
[6]Zhong B,Yang Y,Li S,et al.The adaptor protein MITAlinks virus-sensing receptors to IRF3 transcription factoractivation[J].Immunity,2008,29(4):538-550.
[7]Jin L,Waterman PM,Jonscher KR,et al.MPYS,a novelmembrane tetraspanner,is associated with majorhistocompatibility complex class II and mediatestransduction of apoptotic signals[J].Mol Cell Biol,2008,28(16):5014-5026.
[8]Sun W,Li Y,Chen L,et al.ERIS,an endoplasmicreticulum IFN stimulator,activates innate immunesignaling through dimerization[J].Proc Natl Acad Sci USA,2009,106(21):8653-8658.
[9]Burdette DL,Monroe KM,Sotelo Troha K,et al.STING is adirect innate immune sensor of cyclic di-GMP[J].Nature,2011,478(7370):515-518.
[10]Muruve DA,Petrilli V,Zaiss AK,et al.The inflammasomerecognizes cytosolic microbial and host DNA and triggersan innate immune response[J].Nature,2008,452(7183):103-107.
[11]Barbalat R,Ewald SE,Mouchess ML,et al.Nucleic acidrecognition by the innate immune system[J].Annu RevImmunol,2011,29:185-214.
[12]Unterholzner L,Keating SE,Baran M,et al.IFI16 is aninnate immune sensor for intracellular DNA[J].NatImmunol,2010,11(11):997-1004.
[13]Zhang Z,Yuan B,Bao M,et al.The helicase DDX41 sensesintracellular DNA mediated by the adaptor STING indendritic cells[J].Nat Immunol,2011,12(10):959-965.
[14]Hornung V,Ellegast J,Kim S,et al.5'-Triphosphate RNAis the ligand for RIG-I[J].Science,2006,314(5801):994-997.
[15]Baum A,Sachidanandam R,Garcia Sastre A.Preference ofRIG-I for short viral RNA molecules in infected cellsrevealed by next-generation sequencing[J].Proc Natl AcadSci USA,2010,107(37):16303-16308.
[16]Yoneyama M,Fujita T.RNA recognition and signaltransduction by RIG-I-like receptors[J].Immunol Rev,2009,227(1):54-65.
[17]Jin L,Hill KK,Filak H,et al.MPYS is required for IFNresponse factor 3 activation and type I IFN production inthe response of cultured phagocytes to bacterial secondmessengers cyclic-di-AMP and cyclic-di-GMP[J].JImmunol,2011,187(5):2595-2601.
[18]Menetret JF,Hegde RS,Heinrich SU,et al.Architecture ofthe ribosome-channel complex derived from nativemembranes[J].J Mol Biol,2005,348(2):445-457.
[19]Zhong B,Zhang L,Lei C,et al.The ubiquitin ligase RNF5regulates antiviral responses by mediating degradation ofthe adaptor protein MITA[J].Immunity,2009,30(3):397-407.
[20]Younger JM,Chen L,Ren HY,et al.Sequential quality-control checkpoints triage misfolded cystic fibrosistransmembrane conductance regulator[J].Cell,2006,126(3):571-582.
[21]Wacher C,Muller M,Hofer MJ,et al.Coordinatedregulation and widespread cellular expression ofinterferon-stimulated genes(ISG)ISG-49,ISG-54,andISG-56 in the central nervous system after infection withdistinct viruses[J].J Virol,2007,81(2):860-871.
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[23]Munoz Jordan JL,Laurent Rolle M,Ashour J,et al.Inhibition of alpha/beta interferon signaling by the NS4Bprotein of flaviviruses[J].J Virol,2005,79(13):8004-8013.
[24]Jin L,Xu LG,Yang IV,et al.Identification andcharacterization of a loss-of-function human MPYSvariant[J].Genes Immun,2011,12(4):263-269
[25]Ishii KJ,Kawagoe T,Koyama S,et al.TANK-bindingkinase-1 delineates innate and adaptive immune responsesto DNA vaccines[J].Nature,2008,451(7179):725-729.
[26]Spies B,Hochrein H,Vabulas M,et al.Vaccination withplasmid DNA activates dendritic cells via Toll-likereceptor 9(TLR9)but functions in TLR9-deficient mice[J].J Immunol,2003,171(11):5908-5912.
[27]Chen H,Sun H,You F,et al.Activation of STAT6 bySTING is critical for antiviral innate immunity[J].Cell,2011,147(2):436-446.