The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling

Molecular Cell

Volumn 54, Issue 2, 2014, Pages 289-296

  Cai, Xin ^a   Chiu, Yu Hsin ^b   Chen, Zhijian J ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIC AMP; CYCLIC GMP; CYCLIC GMP AMP SYNTHASE; EXTRACHROMOSOMAL DNA; PROTEIN; STING PROTEIN; UNCLASSIFIED DRUG;

AUTOIMMUNE DISEASE; AUTOIMMUNITY; CELL TYPE; CYTOSOL; DNA SENSING; DNA SEQUENCE; DNA TRANSFECTION; DNA VIRUS; GENE AND NUCLEIC ACID PARAMETERS; HUMAN; IMMUNE RESPONSE; IMMUNITY; IN VIVO STUDY; INNATE IMMUNITY; NONHUMAN; PROTEIN ANALYSIS; REVIEW; SIGNAL TRANSDUCTION;

AUTOIMMUNE DISEASES; CYTOSOL; DNA; HUMANS; IMMUNITY, INNATE; MEMBRANE PROTEINS; MODELS, IMMUNOLOGICAL; MODELS, MOLECULAR; NUCLEOTIDES, CYCLIC; NUCLEOTIDYLTRANSFERASES; SIGNAL TRANSDUCTION;

EID: 84899131835     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2014.03.040     Document Type: Review

References (63)

1. Ablasser A., Goldeck M., Cavlar T., Deimling T., Witte G., Röhl I., Hopfner K.P., Ludwig J., Hornung V. cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING. Nature 2013, 498:380-384.
2. Ablasser A., Schmid-Burgk J.L., Hemmerling I., Horvath G.L., Schmidt T., Latz E., Hornung V. Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature 2013, 503:530-534.
3. Ahn J., Gutman D., Saijo S., Barber G.N. STING manifests self DNA-dependent inflammatory disease. Proc. Natl. Acad. Sci. USA 2012, 109:19386-19391.
4. Burdette D.L., Vance R.E. STING and the innate immune response to nucleic acids in the cytosol. Nat. Immunol. 2013, 14:19-26.
5. Burdette D.L., Monroe K.M., Sotelo-Troha K., Iwig J.S., Eckert B., Hyodo M., Hayakawa Y., Vance R.E. STING is a direct innate immune sensor of cyclic di-GMP. Nature 2011, 478:515-518.
6. Civril F., Deimling T., de Oliveira Mann C.C., Ablasser A., Moldt M., Witte G., Hornung V., Hopfner K.P. Structural mechanism of cytosolic DNA sensing by cGAS. Nature 2013, 498:332-337.
7. Crow Y.J., Hayward B.E., Parmar R., Robins P., Leitch A., Ali M., Black D.N., van Bokhoven H., Brunner H.G., Hamel B.C., et al. Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus. Nat. Genet. 2006, 38:917-920.
8. Diner E.J., Burdette D.L., Wilson S.C., Monroe K.M., Kellenberger C.A., Hyodo M., Hayakawa Y., Hammond M.C., Vance R.E. The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell Rep 2013, 3:1355-1361.
9. Gall A., Treuting P., Elkon K.B., Loo Y.M., Gale M., Barber G.N., Stetson D.B. Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity 2012, 36:120-131.
10. Gao D., Wu J., Wu Y.T., Du F., Aroh C., Yan N., Sun L., Chen Z.J. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science 2013, 341:903-906.
11. Gao P., Ascano M., Wu Y., Barchet W., Gaffney B.L., Zillinger T., Serganov A.A., Liu Y., Jones R.A., Hartmann G., et al. Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase. Cell 2013, 153:1094-1107.
12. Gao P., Ascano M., Zillinger T., Wang W., Dai P., Serganov A.A., Gaffney B.L., Shuman S., Jones R.A., Deng L., et al. Structure-function analysis of STING activation by c[G(2',5')pA(3',5')p] and targeting by antiviral DMXAA. Cell 2013, 154:748-762.
13. Gehrke N., Mertens C., Zillinger T., Wenzel J., Bald T., Zahn S., Tüting T., Hartmann G., Barchet W. Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing. Immunity 2013, 39:482-495.
14. Gough D.J., Messina N.L., Clarke C.J., Johnstone R.W., Levy D.E. Constitutive type I interferon modulates homeostatic balance through tonic signaling. Immunity 2012, 36:166-174.
15. Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., Matsumoto M., Hoshino K., Wagner H., Takeda K., Akira S. A Toll-like receptor recognizes bacterial DNA. Nature 2000, 408:740-745.
16. Huang Y.H., Liu X.Y., Du X.X., Jiang Z.F., Su X.D. The structural basis for the sensing and binding of cyclic di-GMP by STING. Nat. Struct. Mol. Biol. 2012, 19:728-730.
17. Ishii K.J., Coban C., Kato H., Takahashi K., Torii Y., Takeshita F., Ludwig H., Sutter G., Suzuki K., Hemmi H., et al. A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA. Nat. Immunol. 2006, 7:40-48.
18. Ishikawa H., Barber G.N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 2008, 455:674-678.
19. Ishikawa H., Ma Z., Barber G.N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 2009, 461:788-792.
20. Jakobsen M.R., Bak R.O., Andersen A., Berg R.K., Jensen S.B., Tengchuan J., Laustsen A., Hansen K., Ostergaard L., Fitzgerald K.A., et al. IFI16 senses DNA forms of the lentiviral replication cycle and controls HIV-1 replication. Proc. Natl. Acad. Sci. USA 2013, 110:E4571-E4580.
21. Kawane K., Fukuyama H., Kondoh G., Takeda J., Ohsawa Y., Uchiyama Y., Nagata S. Requirement of DNase II for definitive erythropoiesis in the mouse fetal liver. Science 2001, 292:1546-1549.
22. Konno H., Konno K., Barber G.N. Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell 2013, 155:688-698.
23. Kranzusch P.J., Lee A.S., Berger J.M., Doudna J.A. Structure of human cGAS reveals a conserved family of second-messenger enzymes in innate immunity. Cell Rep 2013, 3:1362-1368.
24. Krug A., Luker G.D., Barchet W., Leib D.A., Akira S., Colonna M. Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 2004, 103:1433-1437.
25. Lahaye X., Satoh T., Gentili M., Cerboni S., Conrad C., Hurbain I., ElMarjou A., Lacabaratz C., Lelièvre J.D., Manel N. The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells. Immunity 2013, 39:1132-1142.
26. Lam E., Stein S., Falck-Pedersen E. Adenovirus detection by the cGAS/STING/TBK1 DNA sensing cascade. J.Virol. 2014, 88:974-981.
27. Li X., Shu C., Yi G., Chaton C.T., Shelton C.L., Diao J., Zuo X., Kao C.C., Herr A.B., Li P. Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization. Immunity 2013, 39:1019-1031.
28. Li X.D., Wu J., Gao D., Wang H., Sun L., Chen Z.J. Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. Science 2013, 341:1390-1394.
29. Liang Q., Seo G.J., Choi Y.J., Kwak M.-J., Ge J., Rodgers M.A., Shi M., Leslie B.J., Hopfner K.-P., Ha T., et al. Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses. Cell Host Microbe 2014, 15:228-238.
30. Manel N., Littman D.R. Hiding in plain sight: how HIV evades innate immune responses. Cell 2011, 147:271-274.
31. Manel N., Hogstad B., Wang Y., Levy D.E., Unutmaz D., Littman D.R. A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature 2010, 467:214-217.
32. Manzanillo P.S., Shiloh M.U., Portnoy D.A., Cox J.S. Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages. Cell Host Microbe 2012, 11:469-480.
33. Monroe K.M., Yang Z., Johnson J.R., Geng X., Doitsh G., Krogan N.J., Greene W.C. IFI16 DNA sensor is required for death of lymphoid CD4 Tcells abortively infected with HIV. Science 2014, 343:428-432.
34. O'Neill L.A. DNA makes RNA makes innate immunity. Cell 2009, 138:428-430.
35. O'Neill L.A. Immunology. Sensing the dark side of DNA. Science 2013, 339:763-764.
36. Ouyang S., Song X., Wang Y., Ru H., Shaw N., Jiang Y., Niu F., Zhu Y., Qiu W., Parvatiyar K., et al. Structural analysis of the STING adaptor protein reveals a hydrophobic dimer interface and mode of cyclic di-GMP binding. Immunity 2012, 36:1073-1086.
37. Paludan S.R., Bowie A.G. Immune sensing of DNA. Immunity 2013, 38:870-880.
38. Patel S.J., King K.R., Casali M., Yarmush M.L. DNA-triggered innate immune responses are propagated by gap junction communication. Proc. Natl. Acad. Sci. USA 2009, 106:12867-12872.
39. Rasaiyaah J., Tan C.P., Fletcher A.J., Price A.J., Blondeau C., Hilditch L., Jacques D.A., Selwood D.L., James L.C., Noursadeghi M., Towers G.J. HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature 2013, 503:402-405.
40. Rathinam V.A., Vanaja S.K., Fitzgerald K.A. Regulation of inflammasome signaling. Nat. Immunol. 2012, 13:333-342.
41. Rigby R.E., Webb L.M., Mackenzie K.J., Li Y., Leitch A., Reijns M.A., Lundie R.J., Revuelta A., Davidson D.J., Diebold S., et al. RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. EMBO J. 2014, 33:542-558.
42. Römling U., Galperin M.Y., Gomelsky M. Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol. Mol. Biol. Rev. 2013, 77:1-52.
43. Saitoh T., Fujita N., Hayashi T., Takahara K., Satoh T., Lee H., Matsunaga K., Kageyama S., Omori H., Noda T., et al. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc. Natl. Acad. Sci. USA 2009, 106:20842-20846.
44. Schaap P. Cyclic di-nucleotide signaling enters the eukaryote domain. IUBMB Life 2013, 65:897-903.
45. Schoggins J.W., Macduff D.A., Imanaka N., Gainey M.D., Shrestha B., Eitson J.L., Mar K.B., Richardson R.B., Ratushny A.V., Litvak V., et al. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature 2014, 505:691-695.
46. Shang G., Zhu D., Li N., Zhang J., Zhu C., Lu D., Liu C., Yu Q., Zhao Y., Xu S., Gu L. Crystal structures of STING protein reveal basis for recognition of cyclic di-GMP. Nat. Struct. Mol. Biol. 2012, 19:725-727.
47. Sharma S., DeOliveira R.B., Kalantari P., Parroche P., Goutagny N., Jiang Z., Chan J., Bartholomeu D.C., Lauw F., Hall J.P., et al. Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome. Immunity 2011, 35:194-207.
48. Shu C., Yi G., Watts T., Kao C.C., Li P. Structure of STING bound to cyclic di-GMP reveals the mechanism of cyclic dinucleotide recognition by the immune system. Nat. Struct. Mol. Biol. 2012, 19:722-724.
49. Stetson D.B., Medzhitov R. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity 2006, 24:93-103.
50. Stetson D.B., Ko J.S., Heidmann T., Medzhitov R. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 2008, 134:587-598.
51. Sun L., Wu J., Du F., Chen X., Chen Z.J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 2013, 339:786-791.
52. Sze A., Belgnaoui S.M., Olagnier D., Lin R., Hiscott J., van Grevenynghe J. Host restriction factor SAMHD1 limits human Tcell leukemia virus type 1 infection of monocytes via STING-mediated apoptosis. Cell Host Microbe 2013, 14:422-434.
53. Takeuchi O., Akira S. Pattern recognition receptors and inflammation. Cell 2010, 140:805-820.
54. Tanaka Y., Chen Z.J. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci. Signal. 2012, 5:ra20.
55. Topalian S.L., Drake C.G., Pardoll D.M. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr. Opin. Immunol. 2012, 24:207-212.
56. Topalian S.L., Hodi F.S., Brahmer J.R., Gettinger S.N., Smith D.C., McDermott D.F., Powderly J.D., Carvajal R.D., Sosman J.A., Atkins M.B., et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N.Engl. J. Med. 2012, 366:2443-2454.
57. Wu J., Sun L., Chen X., Du F., Shi H., Chen C., Chen Z.J. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 2013, 339:826-830.
58. Yan N., Regalado-Magdos A.D., Stiggelbout B., Lee-Kirsch M.A., Lieberman J. The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. Nat. Immunol. 2010, 11:1005-1013.
59. Yin Q., Tian Y., Kabaleeswaran V., Jiang X., Tu D., Eck M.J., Chen Z.J., Wu H. Cyclic di-GMP sensing via the innate immune signaling protein STING. Mol. Cell 2012, 46:735-745.
60. Yoshida H., Okabe Y., Kawane K., Fukuyama H., Nagata S. Lethal anemia caused by interferon-beta produced in mouse embryos carryingundigested DNA. Nat. Immunol. 2005, 6:49-56.
61. Zhang X., Shi H., Wu J., Zhang X., Sun L., Chen C., Chen Z.J. Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol. Cell 2013, 51:226-235.
62. Zhang X., Wu J., Du F., Xu H., Sun L., Chen Z., Brautigam C.A., Zhang X., Chen Z.J. The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop. Cell Rep 2014, 6:421-430.
63. Zhong B., Yang Y., Li S., Wang Y.Y., Li Y., Diao F., Lei C., He X., Zhang L., Tien P., Shu H.B. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 2008, 29:538-550.