STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity

Ishikawa, Hiroki; Ma, Zhe; Barber, Glen N.

doi:10.1038/nature08476

Cited by 2,759interferon and immune responsesImmune Response and InflammationImmunotherapy and Immune Responses

STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity

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Ishikawa, Hiroki, Ma, Zhe, Barber, Glen N.·2009·Nature

DOI 10.1038/nature08476PMC PMC4664154

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Abstract

The innate immune system is critical for the early detection of invading pathogens and for initiating cellular host defence countermeasures, which include the production of type I interferon (IFN). However, little is known about how the innate immune system is galvanized to respond to DNA-based microbes. Here we show that STING (stimulator of interferon genes) is critical for the induction of IFN by non-CpG intracellular DNA species produced by various DNA pathogens after infection. Murine embryonic fibroblasts, as well as antigen presenting cells such as macrophages and dendritic cells (exposed to intracellular B-form DNA, the DNA virus herpes simplex virus 1 (HSV-1) or bacteria Listeria monocytogenes), were found to require STING to initiate effective IFN production. Accordingly, Sting-knockout mice were susceptible to lethal infection after exposure to HSV-1. The importance of STING in facilitating DNA-mediated innate immune responses was further evident because cytotoxic T-cell responses induced by plasmid DNA vaccination were reduced in Sting-deficient animals. In the presence of intracellular DNA, STING relocalized with TANK-binding kinase 1 (TBK1) from the endoplasmic reticulum to perinuclear vesicles containing the exocyst component Sec5 (also known as EXOC2). Collectively, our studies indicate that STING is essential for host defence against DNA pathogens such as HSV-1 and facilitates the adjuvant activity of DNA-based vaccines.

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TBK1 activates NF-κB to induce expression of interferon and inflammatory cytokines.
“TBK1 also activates NF‐κB to induce expression of IFN and inflammatory cytokines.65, 66, 67”
From Cellular senescence and senescence-associated secretory phenotype via the cGAS-STING signaling pathway in cancer (2020) · cites this paper as [66]
The paper’s main text (indexed under Abstract; page unavailable) links STING–TBK1 complexes to type I IFN production after intracellular DNA stimulation. It also reports defective NF-κB signalling and reduced IL6 production when STING is absent, but does not establish that TBK1 activates NF-κB to induce IFN and inflammatory cytokines. (LLM, conf=0.84)
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Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888 · see citing works
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Seth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005) · Cell · doi:10.1016/j.cell.2005.08.012 · Cited by 3,329 · see citing works
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Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., & Fitzgerald, K. A. (2009) · Nature · doi:10.1038/nature07725 · Cited by 2,627 · see citing works
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Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005) · Nature · doi:10.1038/nature04193 · Cited by 2,401 · see citing works
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Xu, L., Wang, Y., Han, K.-J., Li, L., Zhai, Z., & Shu, H. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.08.014 · Cited by 1,849 · see citing works
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Zhong, B., Yang, Y., Li, S., Wang, Y., Li, Y., Diao, F., Lei, C., He, X., Zhang, L., Tien, P., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.09.003 · Cited by 1,513 · see citing works
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Chiu, Y., MacMillan, J. B., & Chen, Z. J. (2009) · Cell · doi:10.1016/j.cell.2009.06.015 · Cited by 1,185 · see citing works
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Muruve, D. A., Pétrilli, V., Zaiss, A. K., White, L. R., Clark, S. A., Ross, P. J., Parks, R. J., & Tschopp, J. (2008) · Nature · doi:10.1038/nature06664 · Cited by 936 · see citing works
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Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA
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RalB GTPase-Mediated Activation of the IκB Family Kinase TBK1 Couples Innate Immune Signaling to Tumor Cell Survival
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Spies, B., Hochrein, H., Vabulas, M., Huster, K. M., Busch, D. H., Schmitz, F., Heit, A., & Wagner, H. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.11.5908 · Cited by 196 · see citing works
Ral-regulated interaction between Sec5 and paxillin targets Exocyst to focal complexes during cell migration
Spiczka, K. S., & Yeaman, C. A. (2008) · Journal of Cell Science · doi:10.1242/jcs.031641 · Cited by 111 · see citing works
Single Copies of Sec61 and TRAP Associate with a Nontranslating Mammalian Ribosome
Ménétret, J., Hegde, R. S., Aguiar, M., Gygi, S. P., Park, E., Rapoport, T. A., & Akey, C. W. (2008) · Structure · doi:10.1016/j.str.2008.05.003 · Cited by 101 · see citing works
Recognition of nucleic acid and nucleic acid analogs by Toll-like receptors 7, 8 and 9
Bauer, S., Pigisch, S., Hangel, D., Kaufmann, A. M., & Hamm, S. (2007) · Immunobiology · doi:10.1016/j.imbio.2007.10.010 · Cited by 74 · see citing works
Processing of Human Cytomegalovirus UL37 Mutant Glycoproteins in the Endoplasmic Reticulum Lumen prior to Mitochondrial Importation
Mavinakere, M. S., Williamson, C. D., Goldmacher, V. S., & Colberg‐Poley, A. M. (2006) · Journal of Virology · doi:10.1128/jvi.00492-06 · Cited by 34 · see citing works
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Spiczka, K. S., & Yeaman, C. A. (2008) · Cited by 31 · see citing works

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Liu, S., Cai, X., Wu, J., Cong, Q., Chen, X., Li, T., Du, F., Ren, J., Wu, Y.-T., Grishin, N. V., et al. (2015) · Science · doi:10.1126/science.aaa2630 · Cited by 1,927 · see citing works
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Ablasser, A., Goldeck, M., Cavlar, T., Deimling, T., Witte, G., Röhl, I., Hopfner, K.-P., Ludwig, J., & Hornung, V. (2013) · Nature · doi:10.1038/nature12306 · Cited by 1,695 · see citing works
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STING Specifies IRF3 Phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway
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Fuertes, M. B., Kacha, A. K., Kline, J., Woo, S.-R., Kranz, D. M., Murphy, K. M., & Gajewski, T. F. (2011) · Journal of Experimental Medicine · doi:10.1084/jem.20101159 · Cited by 1,192 · see citing works
Innate Immune Sensing and Signaling of Cytosolic Nucleic Acids
Wu, J., & Chen, Z. J. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120156 · Cited by 1,179 · see citing works
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Haag, S. M., Gulen, M. F., Reymond, L., Gibelin, A., Abrami, L., Decout, A., Heymann, M., van der Goot, F. G., Turcatti, G., Behrendt, R., et al. (2018) · Nature · doi:10.1038/s41586-018-0287-8 · Cited by 1,178 · see citing works
Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects
Li, X.-D., Wu, J., Gao, D., Wang, H., Sun, L., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1244040 · Cited by 1,097 · see citing works
cGAS in action: Expanding roles in immunity and inflammation
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Radiotherapy and immunotherapy: a beneficial liaison?
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The cGAS-cGAMP-STING Pathway of Cytosolic DNA Sensing and Signaling
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Harnessing innate immunity in cancer therapy
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Design of amidobenzimidazole STING receptor agonists with systemic activity
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The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells
Zhang, Z., Yuan, B., Bao, M., Lu, N., Kim, T., & Liu, Y. (2011) · Nature Immunology · doi:10.1038/ni.2091 · Cited by 874 · see citing works
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Rongvaux, A., Jackson, R., Harman, C. C. D., Li, T., West, A. P., de Zoete, M. R., Wu, Y., Yordy, B., Lakhani, S. A., Kuan, C.-Y., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.037 · Cited by 847 · see citing works
Cytosolic Sensing of Viruses
Goubau, D., Deddouche, S., & Sousa, C. R. E. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.007 · Cited by 847 · see citing works
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Zhang, X., Bai, X., & Chen, Z. J. (2020) · Immunity · doi:10.1016/j.immuni.2020.05.013 · Cited by 845 · see citing works
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Saitoh, T., Fujita, N., Hayashi, T., Takahara, K., Satoh, T., Lee, H., Matsunaga, K., Kageyama, S., Omori, H., Noda, T., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911267106 · Cited by 854 · see citing works
Extracellular M. tuberculosis DNA Targets Bacteria for Autophagy by Activating the Host DNA-Sensing Pathway
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The innate immune DNA Sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING.
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. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.05.009 · Cited by 767 · see citing works
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CD47 blockade triggers T cell–mediated destruction of immunogenic tumors
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Rathinam, V. A. K., Vanaja, S. K., Waggoner, L., Sokolovska, A., Becker, C., Stuart, L. M., Leong, J. M., & Fitzgerald, K. A. (2012) · Cell · doi:10.1016/j.cell.2012.07.007 · Cited by 729 · see citing works
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Mukai, K., Konno, H., Akiba, T., Uemura, T., Waguri, S., Kobayashi, T., Barber, G. N., Arai, H., & Taguchi, T. (2016) · Nature Communications · doi:10.1038/ncomms11932 · Cited by 733 · see citing works
Self-citation
Cancer vaccines as promising immuno-therapeutics: platforms and current progress
Liu, J., Fu, M., Wang, M., Wan, D., Wei, Y., & Wei, X. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01247-x · Cited by 725 · see citing works
The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment
Bakhoum, S. F. W., & Cantley, L. C. (2018) · Cell · doi:10.1016/j.cell.2018.08.027 · Cited by 717 · see citing works
The cGAS–STING pathway and cancer
Samson, N., & Ablasser, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00468-w · Cited by 705 · see citing works
Cyclic Dinucleotides Trigger ULK1 (ATG1) Phosphorylation of STING to Prevent Sustained Innate Immune Signaling
Konno, H., Konno, K., & Barber, G. N. (2013) · Cell · doi:10.1016/j.cell.2013.09.049 · Cited by 676 · see citing works
Self-citation
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Shae, D., Becker, K. W., Christov, P. P., Yun, D. S., Lytton‐Jean, A. K. R., Sevimli, S., Ascano, M., Kelley, M. C., Johnson, D. B., Balko, J. M., et al. (2019) · Nature Nanotechnology · doi:10.1038/s41565-018-0342-5 · Cited by 681 · see citing works
MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond
Vance, J. E. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.11.014 · Cited by 665 · see citing works
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Li, X., Shu, C., Yi, G., Chaton, C. T., Shelton, C. L., Diao, J., Zuo, X., Kao, C. C., Herr, A. B., & Li, P. (2013) · Immunity · doi:10.1016/j.immuni.2013.10.019 · Cited by 656 · see citing works
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Ablasser, A., Schmid-Burgk, J. L., Hemmerling, I., Horvath, G. L., Schmidt, T., Latz, E., & Hornung, V. (2013) · Nature · doi:10.1038/nature12640 · Cited by 649 · see citing works
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Dobbs, N., Burnaevskiy, N., Chen, D., Gonugunta, V. K., Alto, N. M., & Yan, N. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.07.001 · Cited by 638 · see citing works
Post-Translational Modification Control of Innate Immunity
Liu, J., Qian, C., & Cao, X. (2016) · Immunity · doi:10.1016/j.immuni.2016.06.020 · Cited by 632 · see citing works
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Marcus, A., Mao, A. J., Lensink-Vasan, M., Wang, L., Vance, R. E., & Raulet, D. H. (2018) · Immunity · doi:10.1016/j.immuni.2018.09.016 · Cited by 609 · see citing works
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Ning, S., Pagano, J. S., & Barber, G. N. (2011) · Genes and Immunity · doi:10.1038/gene.2011.21 · Cited by 590 · see citing works
Self-citation
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Xia, T., Konno, H., Ahn, J., & Barber, G. N. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.029 · Cited by 589 · see citing works
Self-citation
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Schlee, M., & Hartmann, G. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.78 · Cited by 587 · see citing works
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Maekawa, H., Inoue, T., Ouchi, H., Jao, T.-M., Inoue, R., Nishi, H., Fujii, R., Ishidate, F., Tanaka, T., Tanaka, Y., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.050 · Cited by 586 · see citing works
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Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577 · see citing works
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Yum, S., Li, M., Fang, Y., & Chen, Z. J. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2100225118 · Cited by 578 · see citing works
IRF3 and type I interferons fuel a fatal response to myocardial infarction
King, K. R., Aguirre, A. D., Ye, Y., Sun, Y., Roh, J. D., Ng, R. P., Köhler, R. H., Arlauckas, S. P., Iwamoto, Y., Savol, A. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4428 · Cited by 571 · see citing works
Quantitative proteomics reveals subset-specific viral recognition in dendritic cells
Luber, C. A., Cox, J., Lauterbach, H., Fancke, B., Selbach, M., Tschopp, J., Akira, S., Wiegand, M., Hochrein, H., O'Keeffe, M., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.01.013 · Cited by 576 · see citing works
Structures of the HIN Domain:DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor
Jin, T., Perry, A., Jiang, J., Smith, P. T., Curry, J. A., Unterholzner, L., Jiang, Z., Horvath, G. L., Rathinam, V. A. K., Johnstone, R. W., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.02.014 · Cited by 571 · see citing works
Decoding type I and III interferon signalling during viral infection
Mesev, E. V., LeDesma, R. A., & Ploss, A. (2019) · Nature Microbiology · doi:10.1038/s41564-019-0421-x · Cited by 538 · see citing works
Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations
Jeremiah, N., Neven, B., Gentili, M., Callebaut, I., Maschalidi, S., Stolzenberg, M.-C., Goudin, N., Frémond, M.-L., Nitschke, P., Molina, T. J., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci79100 · Cited by 562 · see citing works
Antitumor activity of a systemic STING-activating non-nucleotide cGAMP mimetic
Chin, E. N., Yu, C., Vartabedian, V. F., Jia, Y., Kumar, M. N. S., Gamo, A. M., Vernier, W. F., Ali, S. H., Kissai, M., Lazar, D. C., et al. (2020) · Science · doi:10.1126/science.abb4255 · Cited by 560 · see citing works
Ubiquitin chain diversity at a glance
Akutsu, M., Đikić, I., & Bremm, A. (2016) · Journal of Cell Science · doi:10.1242/jcs.183954 · Cited by 555 · see citing works
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Jarosz–Biej, M., Smolarczyk, R., Cichoń, T., & Kułach, N. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133212 · Cited by 549 · see citing works
TheN-Ethyl-N-Nitrosourea-InducedGoldenticketMouse Mutant Reveals an Essential Function ofStingin theIn VivoInterferon Response toListeria monocytogenesand Cyclic Dinucleotides
Sauer, J., Troha, K., von Moltke, J., Monroe, K. M., Rae, C. S., Brubaker, S. W., Hyodo, M., Hayakawa, Y., Woodward, J. J., Portnoy, D. A., et al. (2010) · Infection and Immunity · doi:10.1128/iai.00999-10 · Cited by 540 · see citing works
DNA released from dying host cells mediates aluminum adjuvant activity
Marichal, T., Ohata, K., Bedoret, D., Mesnil, C., Sabatel, C. M., Kobiyama, K., Lekeux, P. M., Coban, C., Akira, S., Ishii, K. J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2403 · Cited by 538 · see citing works
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Cohen, D., Melamed, S., Millman, A., Shulman, G., Oppenheimer‐Shaanan, Y., Kacen, A., Doron, S., Amitai, G., & Sorek, R. (2019) · Nature · doi:10.1038/s41586-019-1605-5 · Cited by 537 · see citing works
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Yan, N., Regalado-Magdos, A. D., Stiggelbout, B., Lee‐Kirsch, M. A., & Lieberman, J. (2010) · Nature Immunology · doi:10.1038/ni.1941 · Cited by 522 · see citing works
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Monroe, K. M., Yang, Z., Johnson, J. R., Geng, X., Doitsh, G., Krogan, N. J., & Greene, W. C. (2014) · Science · doi:10.1126/science.1243640 · Cited by 511 · see citing works
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Galluzzi, L., Yamazaki, T., & Kroemer, G. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0068-0 · Cited by 529 · see citing works
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Aguirre, S., Maestre, A. M., Pagni, S. E., Patel, J. R., Savage, T. J., Gutman, D. M., Maringer, K., Bernal‐Rubio, D., Shabman, R. S., Simon, V. R., et al. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002934 · Cited by 525 · see citing works
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Nagata, S., & Tanaka, M. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2016.153 · Cited by 518 · see citing works
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Ahn, J., Gutman, D. M., Saijo, S., & Barber, G. N. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215006109 · Cited by 512 · see citing works
Self-citation
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Self-citation
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Gulen, M. F., Koch, U., Haag, S. M., Schuler, F., Apetoh, L., Villunger, A., Radtke, F., & Ablasser, A. (2017) · Nature Communications · doi:10.1038/s41467-017-00573-w · Cited by 505 · see citing works
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Burdette, D. L., & Vance, R. E. (2013) · Nature Immunology · doi:10.1038/ni.2491 · Cited by 501 · see citing works
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Balka, K. R., Louis, C., Saunders, T. L., Smith, A. M., Calleja, D. J., D’Silva, D. B., Moghaddas, F., Tailler, M., Lawlor, K. E., Zhan, Y., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.056 · Cited by 488 · see citing works
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Horner, S. M., Liu, H. M., Park, H. S., Briley, J. D., & Gale, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110133108 · Cited by 492 · see citing works
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Prabakaran, T., Bodda, C., Krapp, C., Zhang, B., Christensen, M. H., Sun, C., Reinert, L. S., Cai, Y., Jensen, S. B., Skouboe, M. K., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201797858 · Cited by 478 · see citing works
Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis
Jones, J. W. M., Kayagaki, N., Brož, P., Henry, T., Newton, K., O’Rourke, K. M., Chan, S. B., Dong, J. J., Qu, Y., Roose-Girma, M., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003738107 · Cited by 487 · see citing works
Oxidative Damage of DNA Confers Resistance to Cytosolic Nuclease TREX1 Degradation and Potentiates STING-Dependent Immune Sensing
Gehrke, N., Mertens, C., Zillinger, T., Wenzel, J., Bald, T., Zahn, S., Tüting, T., Hartmann, G., & Barchet, W. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.004 · Cited by 476 · see citing works
Mycobacterium Tuberculosis Activates the DNA-Dependent Cytosolic Surveillance Pathway within Macrophages
Manzanillo, P. S., Shiloh, M. U., Portnoy, D. A., & Cox, J. S. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.03.007 · Cited by 456 · see citing works
HIV-1 evades innate immune recognition through specific cofactor recruitment
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., et al. (2013) · Nature · doi:10.1038/nature12769 · Cited by 465 · see citing works
Newly described pattern recognition receptors team up against intracellular pathogens
Brož, P., & Monack, D. M. (2013) · Nature reviews. Immunology · doi:10.1038/nri3479 · Cited by 459 · see citing works
Viral evasion of intracellular DNA and RNA sensing
Chan, Y., & Gack, M. U. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.45 · Cited by 451 · see citing works
The Interferon (IFN) Class of Cytokines and the IFN Regulatory Factor (IRF) Transcription Factor FamilyPreprint
Negishi, H., Taniguchi, T., & Yanai, H. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028423 · Cited by 447 · see citing works

STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
Ishikawa, H., & Barber, G. N. (2008) · Nature · doi:10.1038/nature07317 · Cited by 3,576 · see citing works
Self-citation
STING an essential trigger of DNA-mediated innate immune signaling. (P1258)
Barber, G. N. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.190.supp.116.7
Self-citation
Cellular and Molecular Life Sciences REVIEW The STING pathway and regulation of innate immune signaling in response to DNA pathogens
Ishikawa, H., Barber, G. N., & Barber, H. I. G. N. (2013)
Self-citation
STING-ing the Antiviral Pathway
Nakhaei, P., Hiscott, J. B., & Lin, R. (2009) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjp048 · Cited by 50 · see citing works
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455:674–8. doi: 10.1038/nature07317
Ishikawa, H., & Barber, G. N. (2008)
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Authors: Ishikawa, H., Ma, Z., & Barber, G. N.
Affiliations: University of Miami (US)
Corresponding author: Barber, Glen N.
ORCID: Ishikawa, Hiroki
Ma, Zhe
Barber, Glen N.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-09-23
Volume: 461
Issue: 7265
Pages: 788-792
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08476
PMC: PMC4664154
OpenAlex: W1968178474
Semantic Scholar: 1098beb4c76eacfcc093a88d02d02a681585e7c4
Cited by: 2,759
References: 31
Citations by year: 2026: 184 · 2025: 229 · 2024: 240 · 2023: 240 · 2022: 237 · 2021: 249 · 2020: 212 · 2019: 182 · 2018: 147 · 2017: 170 · 2016: 110 · 2015: 118 · 2014: 114 · 2013: 115 · 2012: 78
FWCI: 30.14
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Institutes of Health
National Institute of Allergy and Infectious Diseases (AI079336, R56AI079336, R01AI079336)
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: STING, mita, Eris, type I interferon, innate immunity, herpes simplex virus type 1, TBK1, Sec5, endosomes, DNA vaccine, plasmid DNA immunization, Listeria monocytogenes, viral susceptibility, dendritic cells
MeSH terms: STING Protein, Animals, Antigen-Presenting Cells, DNA, Bacterial, DNA, Viral, Endoplasmic Reticulum, Fibroblasts, Immunity, Innate, Interferon Type I, Listeria monocytogenes, Membrane Proteins, Plasmids, T-Lymphocytes, Cytotoxic, Protein Serine-Threonine Kinases, Herpesvirus 1, Human, Mice, Knockout, Vaccines, DNA, Protein Transport, Cytoplasmic Vesicles, Vesicular Transport Proteins, Intracellular Space, Mice

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STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity

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