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STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Open accessAbstract
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 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]
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Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S., & Fujita, T. (2004) · Nature Immunology · doi:10.1038/ni1087 · Cited by 4,022
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
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
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
Self-citationSeth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005) · Cell · doi:10.1016/j.cell.2005.08.012 · Cited by 3,329
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
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
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005) · Nature Immunology · doi:10.1038/ni1243 · Cited by 2,562
Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005) · Nature · doi:10.1038/nature04193 · Cited by 2,401
VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling
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
AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
Fernandes-Alnemri, T., Yu, J.-W., Datta, P., Wu, J., & Alnemri, E. S. (2009) · Nature · doi:10.1038/nature07710 · Cited by 1,831
DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response
Takaoka, A., Wang, Z., Choi, M. K., Yanai, H., Negishi, H., Ban, T., Lu, Y., Miyagishi, M., Kodama, T., Honda, K., et al. (2007) · Nature · doi:10.1038/nature06013 · Cited by 1,704
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A conserved ion channel function of STING mediates noncanonical autophagy and cell death
Xun, J., Zhang, Z., Lv, B., Lu, D., Yang, H., Shang, G., & Tan, J. X. (2024) · EMBO Reports · doi:10.1038/s44319-023-00045-x · Cited by 119
“The cyclic GMP-AMP (cGAMP) synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathway is critical in host defense against microbial infection (Ishikawa and Barber, 2008; Ishikawa et al, 2009; Sun et al, 2009; Zhong et al, 2008).”
The essential adaptors of innate immune signaling
Chen, H., & Jiang, Z. (2012) · Protein & Cell · doi:10.1007/s13238-012-2063-0 · Cited by 116
“STING-deficient mice are highly sensitive to both RNA viruses, e.g. vesicular stomatitis virus (VSV) and Sendai virus (SeV) and DNA viruses, e.g. herpes simplex virus type I (HSV-1), underscoring the physiological function of STING in antiviral immune responses (Ishikawa et al., 2009).”
BackgroundInfluentialSignaling Organelles of the Innate Immune System
Kagan, J. C. (2012) · Cell · doi:10.1016/j.cell.2012.11.011 · Cited by 120
“Upon DNA transfection or viral infection, STING will move from the ER to poorly characterized vesicles that contain the IRF3 kinase TBK1 (Ishikawa et al., 2009; Saitoh et al., 2009).”
BackgroundInfluentialCoutermarsh‐Ott, S. L., Eden, K. B., & Allen, I. C. (2016) · Journal of General Virology · doi:10.1099/jgv.0.000401 · Cited by 119
“Upon stimulation with intracellular pathogens such as HSV, STING relocalizes from the endoplasmic reticulum to perinuclear vesicles, resulting in IRF3 activation and pro-inflammatory cytokine production (Ishikawa and Barber, 2008; Ishikawa et al., 2009).”
BackgroundSTING regulates metabolic reprogramming in macrophages via HIF-1α during Brucella infection
Gomes, M. T. R., Guimarães, E. S., Marinho, F. V., Macedo, I., Aguiar, E. R. G. R., Barber, G. N., Moraes‐Vieira, P. M., Alves-Filho, J. C., & Oliveira, S. C. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009597 · Cited by 116
“STING is a transmembrane protein that regulates DNA-mediated type I interferon-dependent innate immune responses [22].”
Self-citationUltrathin Clay Nanoparticles‐Mediated Mutual Reinforcement of Ferroptosis and Cancer Immunotherapy
Liu, J., Zhan, J., Zhang, Y., Huang, L., Yang, J., Feng, J., Ding, L., Shen, Z., & Chen, X. S. (2023) · Advanced Materials · doi:10.1002/adma.202309562 · Cited by 114
Lv, H., Zong, Q., Chen, C., Lv, G., Xiang, W., Xing, F., Jiang, G., Yan, B., Sun, X., Ma, Y., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-43743-9 · Cited by 117
“As a cytosolic DNA sensor, cyclic GMP-AMP synthase (cGAS) triggers innate immune responses through production of the second messenger cyclic GMP-AMP (cGAMP), which binds and activates the stimulatorofinterferongenes(STING) 9,10 .”
InfluentialWong, M.-T., & Chen, S. S.-L. (2014) · Cellular and Molecular Immunology · doi:10.1038/cmi.2014.127 · Cited by 121
Koppe, U., Högner, K., Doehn, J.-M., Müller, H. C., Witzenrath, M., Gutbier, B., Bauer, S., Pribyl, T. M., Hammerschmidt, S., Lohmeyer, J., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1004143 · Cited by 113
“Similar to D39 pneumococci, TIGR4 bacteria stimulated IFN a/b production depending on bacterial uptake, PLY, and on the host cell molecules STING and IRF3.”
BackgroundInfluentialVirus-induced humoral immunity: on how B cell responses are initiated
Zabel, F., Kündig, T. M., & Bachmann, M. F. (2013) · Current Opinion in Virology · doi:10.1016/j.coviro.2013.05.004 · Cited by 113
Antigen expression determines adenoviral vaccine potency independent of IFN and STING signaling
Quinn, K. M., Zak, D. E., Costa, A. D. S., Yamamoto, A., Kastenmüller, K., Hill, B. J., Lynn, G. M., Darrah, P. A., Lindsay, R. W. B., Wang, L., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78280 · Cited by 113
Innate Immune Evasion Mediated by Flaviviridae Non-Structural Proteins
Chen, S., Wu, Z., Wang, M., & Cheng, A. (2017) · Viruses · doi:10.3390/v9100291 · Cited by 113
“The MAM is a dynamic structure in which the mitochondria and the MAVS-STING association mainly reside [91,92].”
BackgroundZDHHC18 negatively regulates cGAS‐mediated innate immunity through palmitoylation
Shi, C., Yang, X., Liu, Y., Li, H., Chu, H., Li, G., & Yin, H. H. (2022) · The EMBO Journal · doi:10.15252/embj.2021109272 · Cited by 113
“Next, STING recruits and activates the kinase TANK-binding kinase 1 (TBK1), which in turn phosphorylates STING and IRF3 (Ishikawa et al , 2009; Saitoh et al , 2009; Dobbs et al , 2015).”
Recognition of cytosolic DNA by c GAS and other STING ‐dependent sensors
Bhat, N., & Fitzgerald, K. A. (2013) · European Journal of Immunology · doi:10.1002/eji.201344127 · Cited by 115
Reactive oxygen species oxidize STING and suppress interferon production
Tao, L., Lemoff, A. S., Wang, G., Zarek, C. M., Lowe, A., Yan, N., & Reese, T. A. (2020) · eLife · doi:10.7554/elife.57837 · Cited by 111
“Upon activation, STING undergoes a conformational change and rearranges to form a polymer (Ergun et al., 2019; Ishikawa et al., 2009; Tanaka and Chen, 2012).”
BackgroundSTING, the Endoplasmic Reticulum, and Mitochondria: Is Three a Crowd or a Conversation?
Smith, J. A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.611347 · Cited by 116
“In contrast, Stimulator of Interferon Gene (STING) resides in the endoplasmic reticulum (ER), particularly in ER-mitochondrial appositions, with its triggering face to the cytosol (8).”
BackgroundThe sensing of mitochondrial DAMPs by non-immune cells
Rodríguez‐Nuevo, A., & Antonio Zorzano, A. (2019) · Cell Stress · doi:10.15698/cst2019.06.190 · Cited by 119
Immune Diseases Associated with TREX1 and STING Dysfunction
Yan, N. (2017) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2016.0086 · Cited by 110
Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids
Hu, M.-M., & Shu, H.-B. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062903 · Cited by 110
Zhang, T., Ono, K., Tsutsuki, H., Ihara, H., Islam, W., Akaike, T., & Sawa, T. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.02.003 · Cited by 110
Song, H., Chen, L., Pan, X., Shen, Y., Ye, M., Wang, G., Cui, C., Zhou, Q., Tseng, Y., Gong, Z., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.02.014 · Cited by 120
Damage-associated molecular patterns (DAMPs) in diseases: implications for therapy
Lin, H., Xiong, W. G., Fu, L., Yi, J., & Yang, J. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00305-3 · Cited by 137
Żmurko, J., Neyts, J. H., & Dallmeier, K. (2015) · Reviews in Medical Virology · doi:10.1002/rmv.1835 · Cited by 109
Recognition of Herpes Simplex Viruses: Toll-Like Receptors and Beyond
Ma, Y., & He, B. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.11.012 · Cited by 110
“STING functions as a key adaptor downstream of majority of cytosolic DNA sensors that leads to the type I IFN response [55,56].”
Targeting pattern recognition receptors in cancer immunotherapy
Goutagny, N., Estornes, Y., Hasan, U. A., Lebecque, S., & Caux, C. (2012) · Targeted Oncology · doi:10.1007/s11523-012-0213-1 · Cited by 113
“The activation of these pathways relies on various adaptors downstream of the different PRR: myeloid differentiation factor 88 (MYD88) and toll/IL-1 receptor (TIR) domain-containing adaptor inducing interferon β (TRIF) for TLR, mitochondrial antiviral signaling (MAVS) (also known as IPS1/CARDIF/VISA) for RNA helicases…”
BackgroundThe molecular era of protein S-acylation: spotlight on structure, mechanisms, and dynamics
Zaballa, M.-E., & van der Goot, F. G. (2018) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2018.1488804 · Cited by 109
“In this pathway, the ER receptor protein STING (stimulator of interferon genes) is essential to initiate effective IFN production and trigger the expression of IFN-stimulated genes (Ishikawa et al. 2009).”
BackgroundRoles of the cGAS-STING Pathway in Cancer Immunosurveillance and Immunotherapy
Yum, S., Li, M., Frankel, A. E., & Chen, Z. J. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030518-055636 · Cited by 109
“After cGAMP binding, STING traffics from the ER to the ER-Golgi intermediate compartment and then to the Golgi apparatus (Ishikawa et al. 2009, Saitoh et al. 2009).”
BackgroundStimulator of interferon genes (STING) activation exacerbates experimental colitis in mice
Martin, G. R., Blomquist, C. M., Henare, K. L., & Jirik, F. R. (2019) · Scientific Reports · doi:10.1038/s41598-019-50656-5 · Cited by 109
Exosomes for mRNA delivery: a novel biotherapeutic strategy with hurdles and hope
Aslan, C., Kiaie, S. H., Zolbanin, N. M., Lotfinejad, P., Ramezani, R., Kashanchi, F., & Jafari, R. (2021) · BMC Biotechnology · doi:10.1186/s12896-021-00683-w · Cited by 113
“Studies have shown that STING has not participated in dsRNA (poly IC) signaling, is mostly regulated by RLRs [32].”
BackgroundInfluentialTBK1, a central kinase in innate immune sensing of nucleic acids and beyond
Zhou, R., Zhang, Q., & Xu, P. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa051 · Cited by 104
A new paradigm: innate immune sensing of viruses via the unfolded protein response
Smith, J. A. (2014) · Frontiers in Microbiology · doi:10.3389/fmicb.2014.00222 · Cited by 115
“For instance, Coronavirus antagonizes a molecule in the DNA-sensing pathway, Stimulator of Interferon Gene (STING/MITA) by disrupting its association with the IRF3activating kinase tank binding kinase 1 (TBK1)/IKKε (Ishikawa et al., 2009; Sun et al., 2012).”
InfluentialThe Molecular Basis of Viral Inhibition of IRF- and STAT-Dependent Immune Responses
Chiang, H.-S., & Liu, H. M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2018.03086 · Cited by 108
Zhou, L., Xu, Q., Huang, L., Jin, J., Zuo, X., Zhang, Q., Ye, L., Zhu, S., Zhan, P., Ren, J., et al. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.11.049 · Cited by 109
Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing
Chathuranga, K., Weerawardhana, A., Dodantenna, N., & Lee, J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00691-y · Cited by 110
Ohta, A., & Nishiyama, Y. (2010) · Mitochondrion · doi:10.1016/j.mito.2010.08.006 · Cited by 111
“Ishikawa and colleagues, however, reported that STING was located on the ER (Ishikawa and Barber, 2008) and translocated from ER to Sec-5-containing vesicles in response to HSV-1 infection, suggesting that STING functions in DNA-mediated innate immunity (Ishikawa et al., 2009).”
Intracellular detection of viral nucleic acids
Sparrer, K. M. J., & Gack, M. U. (2015) · Current Opinion in Microbiology · doi:10.1016/j.mib.2015.03.001 · Cited by 105
“Furthermore, studies in STING-knockout mice demonstrated that STING is critical for in vivo protection against herpes simplex virus1 (HSV-1) [57].”
BackgroundBrégnard, C., Guerra, J., Déjardin, S., Passalacqua, F., Benkirane, M., & Laguette, N. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.05.005 · Cited by 112
“Silencing cGAS but not IFI16 led to decreased pro-inflammatory signaling (Fig.”
BackgroundInfluentialChen, Y., Wang, L., Jin, J., Luan, Y., Chen, C., Yu, L., Chu, H., Wang, X., Liao, G., Yu, Y., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20161387 · Cited by 108
ZBP1/DAI Drives RIPK3-Mediated Cell Death Induced by IFNs in the Absence of RIPK1
Ingram, J. P., Thapa, R. J., Fisher, A. D., Tummers, B., Zhang, T., Yin, C., Rodríguez, D. A., Guo, H., Lane, R. K., Williams, R. M., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1900216 · Cited by 108
“Zbp12/2 (7), Ripk12/2 (3), Ripk32/2 (10), Casp82/2 (11), Tnfr12/2 (12), Ifnar12/2 (13), Ifngr12/2 (14), Stat12/2 (15), Sting2/2 (16), and Mavs2/2 (17) mice have been previously described.”
InfluentialFenech, E. J., Lari, F., Charles, P. D., Fischer, R., Laétitia-Thézénas, M., Bagola, K., Paton, A. W., Paton, J. C., Gyrd‐Hansen, M., Kessler, B. M., et al. (2020) · eLife · doi:10.7554/elife.57306 · Cited by 106
Weber, M. M., Lam, J. L., Dooley, C. A., Noriea, N. F., Hansen, B. T., Hoyt, F. H., Carmody, A., Sturdevant, G. L., & Hackstadt, T. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.04.058 · Cited by 106
“The stimulator of interferon genes (STING) is an endoplasmic reticulum membrane protein that is crucial for the induction of interferon in response to cytosolic DNA or cyclic dinucleotides (Ishikawa et al., 2009).”
BackgroundFranco, M. M. C., Marim, F. M., Guimarães, E. S., Assis, N. R. G., Cerqueira, D. M., Alves‐Silva, J., Harms, J. S., Splitter, G. A., Smith, J. A., Kanneganti, T., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700725 · Cited by 107
“phosphorylates IFN regulatory factor (IRF)-3, a transcription factor required for the induction of IFN-b expression (12).”
BackgroundSelf-citationInhibition of the ATM/Chk2 axis promotes cGAS/STING signaling in ARID1A-deficient tumors
Wang, L., Yang, L., Wang, C., Wei, Z., Ju, Z., Zhang, W., Shen, J., Peng, Y., An, C., Luu, Y. T., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci130445 · Cited by 106
“As shown in Supplemental Figure 5, E and F, HU treatment promoted cytosolic DNA and the production of proinflammatory cytokines, including CCL5 and CXCL10, similarly to ATM inhibitor.”
BackgroundInfluentialDeubiquitylating Enzymes in Cancer and Immunity
Ren, J., Yu, P., Liu, S., Li, R., Niu, X., Chen, Y., Zhang, Z., Zhou, F., & Zhang, L. (2023) · Advanced Science · doi:10.1002/advs.202303807 · Cited by 118
Leuzzi, G., Vasciaveo, A., Taglialatela, A., Chen, X., Firestone, T. M., Hickman, A. R., Mao, W., Thakar, T., Vaitsiankova, A., Huang, J., et al. (2024) · Cell · doi:10.1016/j.cell.2024.01.008 · Cited by 113
cGAS-STING pathway mediates activation of dendritic cell sensing of immunogenic tumors
Li, G., Zhao, X., Zheng, Z., Zhang, H., Wu, Y., Shen, Y., & Chen, Q. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05191-6 · Cited by 114
“When cGAS detects DNA, it generates cGAMP, which then activates STING and starts a cascade that results in the creation of IFN-I [9–11].”
BackgroundLindau, D., Mussard, J., Rabsteyn, A., Ribon, M., Kötter, I., Igney-Oertel, A., Adema, G. J., Boissier, M., Rammensee, H., & Decker, P. (2013) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2012-203041 · Cited by 106
A Nuclear Export Signal Is Required for cGAS to Sense Cytosolic DNA
Sun, H., Huang, Y., Mei, S., Xu, F., Liu, X., Zhao, F., Yin, L., Zhang, D., Wei, L., Wu, C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108586 · Cited by 105
Kalamvoki, M., & Roizman, B. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323414111 · Cited by 105
“STING knockout mice were significantly more susceptible to HSV-1 than the normal siblings (18).”
BackgroundBaum, R., Sharma, S., Carpenter, S. B., Li, Q., Busto, P., Fitzgerald, K. A., Marshak‐Rothstein, A., & Gravallese, E. M. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1402573 · Cited by 104
“DKO mice were bred with STING-deficient mice on a B6/129 background (8) or AIM2-deficient mice (9) to yield STING or AIM2 TKO mice.”
Rasmussen, S. B., Horan, K., Holm, C. K., Stranks, A. J., Mettenleiter, T. C., Simon, A. K., Jensen, S. B., Rixon, F. J., He, B., & Paludan, S. R. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100949 · Cited by 108
“How STING is involved in autophagy still has to be elucidated, but given its function as a transmembrane protein involved in membrane dynamics during HSV-1 infection (56), it appears likely that STING is involved in integration of DNA sensing with membrane reorganization.”
BackgroundDorta-Estremera, S. M., Hegde, V. L., Slay, R., Sun, R., Yanamandra, A. V., Nicholas, C., Nookala, S. M. K., Sierra, G., Curran, M. A., & Sastry, K. J. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0728-4 · Cited by 108
cGAS-STING signaling in cancer immunity and immunotherapy
Du, H., Xu, T., & Cui, M. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110972 · Cited by 106
New Insights into the Role of Mitochondria-Associated Endoplasmic Reticulum Membrane
Fujimoto, M., & Hayashi, T. (2011) · International review of cytology · doi:10.1016/b978-0-12-386033-0.00002-5 · Cited by 106
“A recent study also found that stimulator of interferon genes (STING) is critical for the induction of IFN by non-CpG intracellular DNA species produced by various DNA pathogens (Ishikawa et al., 2009).”
Gao, P., Zillinger, T., Wang, W., Ascano, M., Dai, P., Hartmann, G., Tuschl, T., Deng, L., Barchet, W., & Patel, D. J. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.08.010 · Cited by 105
“The endoplasmic reticulum transmembrane protein STING (stimulator of interferon genes) (Ishikawa and Barber, 2008; Ishikawa et al., 2009; Jin et al., 2008; Sun et al., 2009; Zhong et al., 2008) is a central player in the innate immune response to cytosolic double-stranded DNA (Burdette and Vance, 2013).”
Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS
Webb, L. G., Veloz, J., Silva, J. P., Zhu, T., Rangel, M. V., Mutetwa, T., Zhang, L., Bernal‐Rubio, D., Figueroa, D., Carrau, L., et al. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008999 · Cited by 105
“It has been reported that STING interacts with both RIG-I and MAVS and that STING null cells have reduced type-I IFN production when stimulated with vesicular stomatitis virus (VSV) or Sendai virus (SeV)[41, 42, 85].”
BackgroundInfluentialKim, D., Endo, A., Fang, F. G., Huang, K., Bao, X., Choi, H.-W., Majumder, U., Shen, Y., Mathieu, S. R., Zhu, X., et al. (2021) · ChemMedChem · doi:10.1002/cmdc.202100068 · Cited by 108
Lee, K.-G., Kim, S. S.-Y., Kui, L., Voon, D. C., Mauduit, M., Bist, P., Bi, X., Pereira, N. A., Liu, C., Sukumaran, B., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.01.039 · Cited by 104
Innate immune sensing of DNA viruses
Rathinam, V. A. K., & Fitzgerald, K. A. (2011) · Virology · doi:10.1016/j.virol.2011.02.003 · Cited by 102
“The STING-TBK1 axis is central to the cytosolic DNA- and RNA- driven interferon responses and host resistance against DNA viral infections (Ishikawa, Ma, and Barber, 2009).”
BackgroundTargeting DNA repair in cancer: current state and novel approaches
Klinakis, A., Karagiannis, D., & Rampias, T. N. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03299-8 · Cited by 108
“Activated STING triggers phosphorylation and nuclear translocation of IRF3 which in turn activates transcription of inflammatory genes [159, 160].”
Targeting innate sensing in the tumor microenvironment to improve immunotherapy
Liu, Z., Han, C., & Fu, Y. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0341-y · Cited by 105
Deficiency in coatomer complex I causes aberrant activation of STING signalling
Steiner, A., Hrovat-Schaale, K., Prigione, I., Yu, C., Laohamonthonkul, P., Harapas, C. R., Low, R. R. J., Nardo, D. D., Dagley, L. F., Mlodzianoski, M. J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29946-6 · Cited by 118
Swiecki, M. K., Wang, Y., Gilfillan, S., & Colonna, M. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003728 · Cited by 107
STING Promotes Homeostasis via Regulation of Cell Proliferation and Chromosomal Stability
Rañoa, D. R. E., Widau, R. C., Mallon, S., Parekh, A. D., Nicolae, C. M., Huang, X., Bolt, M. J., Arina, A., Parry, R., Kron, S. J., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-1972 · Cited by 103
“STINGdirectlymediates innate immune responses to cyclic dinucleotides produced by intracellular bacteria and viruses (2, 6) as well as the endogenous cyclic dinucleotide cGAMP (c[G(20-50)pA(30-50)p]) (7, 8).”
BackgroundMethodJi, Y., Luo, Y., Wu, Y., Sun, Y., Zhao, L., Xue, Z., Sun, M., Wei, X., He, Z., Wu, S. A., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01138-4 · Cited by 104
“Activated STING exits the ER and translocates to the trans -Golgi network 6,7 , where STING recruits and activates downstream kinase TANK-binding kinase 1 (TBK1) and the transcription factor interferon regulatory factor 3 (IRF3), leading to the induction of key inflammatory cytokine genes involved in innate immunity,…”
InfluentialMolecular and Structural Basis of DNA Sensors in Antiviral Innate Immunity
Zahid, A., Ismail, H., Li, B., & Jin, T. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.613039 · Cited by 100
“org 6 STING is a transmembrane protein expressed by the outer mitochondrial membrane and ER, and it relocalizes with TANK-b ind ing k inase 1 (TBK1) , wh ich execu te s phosphorylation activation of IRF3 and IRF7 (59, 93).”
BackgroundInfluentialRegulating STING in health and disease
Li, Y., Wilson, H. L., & Kiss‐Toth, E. (2017) · Journal of Inflammation · doi:10.1186/s12950-017-0159-2 · Cited by 104
“Activation of STING induces adaptor dimerization [7] and subsequent migration from ER membranes to punctate membranes of the Golgi by mechanisms similar to autophagy [11].”
BackgroundInfluentialInnate Immune Signaling and Its Role in Metabolic and Cardiovascular Diseases
Xu, M. M., Liu, P. P., & Li, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00065.2017 · Cited by 100
A STING to inflammation and autoimmunity
Kumar, V. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.4mir1018-397rr · Cited by 100
Guo, Y., Jiang, F., Kong, L., Wu, H. M., Zhang, H., Chen, X., Zhao, J., Cai, B., Li, Y., Ma, C., et al. (2020) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00531-5 · Cited by 103
Verzosa, A. L., McGeever, L. A., Bhark, S., Delgado, T., Salazar, N., & Sanchez, E. L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.644664 · Cited by 107
Host–Pathogen Interactions During Mycobacterium tuberculosis infections
Stanley, S. A., & Cox, J. S. (2013) · Current topics in microbiology and immunology · doi:10.1007/82_2013_332 · Cited by 106
Malireddi, R. K. S., & Kanneganti, T. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00077 · Cited by 101
“LM-induced type I IFN production is largely independent of TLR signaling and is instead mediated by cytoplasmic RLR- and STING-dependent pathways through the TBK1-IRF3 signaling axis (Ishikawa et al., 2009; Woodward et al., 2010).”
BackgroundHua, X., Li, B., Song, L., Hu, C., Li, X., Wang, D., Xiong, Y., Zhao, P., He, H., Xia, Q., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000194 · Cited by 101
“2B), which was similarly observed for the localization of STING upon viral infection or interferon stimulatory DNA (ISD) transfection in mammalian cells (4).”
BackgroundElion, D. L., & Cook, R. S. (2018) · Oncotarget · doi:10.18632/oncotarget.25626 · Cited by 99
“Synthetic STING ligands potently induce antitumor immunity in several cancers, including breast cancer, chronic lymphocytic leukemia, colon cancer, and squamous cell carcinoma [13–17].”
BackgroundInfluentialSTING Operation at the ER/Golgi Interface
Taguchi, T., Mukai, K., Takaya, E., & Shindo, R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.646304 · Cited by 104
“Treatment with brefeldin A (BFA) or expression of Shigella effector IpaJ, which inhibits the ER-toGolgi traffic, dampens the phosphorylation of IRF3 and induction of IFNb, suggesting that the ER-to-Golgi traffic is required for the STING signaling (13, 21, 23, 24).”
BackgroundAn, C., Sun, F., Liu, C., Huang, S., Xu, T., Zhang, C., & Ge, S. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110795 · Cited by 99
Nucleic Acid Sensors and Type I Interferon Production in Systemic Lupus Erythematosus
Shrivastav, M., & Niewold, T. B. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00319 · Cited by 99
“Initial studies showed that STING also interacted with components of the RNArecognition machinery, such as RIG-I, where it was linked to type I IFN induction in response to VSV, a negative-strand RNA virus (97, 99).”
BackgroundRae, C. S., Geissler, A. L., Adamson, P. C., & Portnoy, D. A. (2011) · Infection and Immunity · doi:10.1128/iai.00077-11 · Cited by 98
“A second pathway is triggered by listerial cyclic di-AMP and stimulates an interferon regulatory factor 3/Sting-dependent response, leading to the expression of beta interferon (IFN- ) and coregulated genes (26, 43, 50, 51, 66).”
BackgroundLuthra, P., Aguirre, S., Yen, B. C., Pietzsch, C. A., Sánchez-Aparicio, M. T., Tigabu, B., Morlock, L., García‐Sastre, A., Leung, D. W., Williams, N. S., et al. (2017) · mBio · doi:10.1128/mbio.00368-17 · Cited by 101
“CDN activates signaling through STING to trigger IFN production (29–31).”
STING palmitoylation as a therapeutic target
Hansen, A. L., Mukai, K., Schopfer, F. J., Taguchi, T., & Holm, C. K. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0205-5 · Cited by 102
cGAS-STING pathway in oncogenesis and cancer therapeutics
Hoong, B. Y. D., Gan, Y., Liu, H., & Chen, E. S. (2020) · Oncotarget · doi:10.18632/oncotarget.27673 · Cited by 106
“Previously, it was thought that STING complexes with TANKbinding kinase 1 (TBK1; also called NF-κB-activating kinase [NAK]) before trafficking from the ER to Sec5containing endosomal compartments via the Golgi [37]; however, it has since been shown that translocation to the Golgi is a prerequisite for STING to bind TB…”
BackgroundInfluentialELAVL1 Primarily Couples mRNA Stability with the 3’UTRs of Interferon Stimulated Genes
Rothamel, K. L., Arcos, S., Kim, B., Reasoner, C., Lisy, S. M., Mukherjee, N., & Ascano, M. (2020) · Cell Reports · doi:10.1016/j.celrep.2021.109178 · Cited by 93
“Importantly, we found that among the most highly regulated targets were transcripts that encode for ISGs and their transcriptional regulators, suggesting that ELAVL1 contributes at multiple levels of a proinflammatory response.”
InfluentialJeon, S., Jeon, Y., Lim, J.-Y., Kim, Y., Cha, B., & Kim, W. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02070-1 · Cited by 105
Innate immunity and tolerance toward mitochondria
Rongvaux, A. (2017) · Mitochondrion · doi:10.1016/j.mito.2017.10.007 · Cited by 115
RAB11-mediated trafficking in host–pathogen interactions
Guichard, A., Nizet, V., & Bier, E. (2014) · Nature Reviews Microbiology · doi:10.1038/nrmicro3325 · Cited by 105
AIM2 Drives Joint Inflammation in a Self-DNA Triggered Model of Chronic Polyarthritis
Jakobs, C., Perner, S., & Hornung, V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131702 · Cited by 103
“For example, expression of IFNβ, a cytokine that is completely STING-dependent in the context of cytosolic DNA recognition [25], was greatly reduced in diseased joints of AIM2-deficient mice.”
BackgroundHerpesviruses hijack host exosomes for viral pathogenesis
Sadeghipour, S., & Mathias, R. A. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.03.005 · Cited by 100
The binding of TBK1 to STING requires exocytic membrane traffic from the ER
Ogawa, E., Mukai, K., Saito, K., Arai, H., & Taguchi, T. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.05.199 · Cited by 101
Stempel, M., Chan, B., Lisnić, V. J., Krmpotić, A., Hartung, J., Paludan, S. R., Füllbrunn, N., Lemmermann, N. A. W., & Brinkmann, M. M. (2019) · The EMBO Journal · doi:10.15252/embj.2018100983 · Cited by 96
“Upon overexpression of cGAS-GFP to activate STING-dependent signaling, we observed that STING translocated to the perinuclear region as described previously (Ishikawa et al , 2009) (Fig 2A, lower panel).”
Prabakaran, T., Troldborg, A., Kumpunya, S., Alee, I., Marinković, E., Windross, S. J., Nandakumar, R., Narita, R., Zhang, B., Carstensen, M., et al. (2021) · EBioMedicine · doi:10.1016/j.ebiom.2021.103314 · Cited by 99
“Finally, the enzyme cGAS detects cytoplasmic DNA and is activated to produce 2 0 3 ’ cGAMP, which acts as a second messenger binding to the ER-resident protein STING [4,22].”
STING agonist cGAMP enhances anti-tumor activity of CAR-NK cells against pancreatic cancer
Da, Y., Liu, Y., Hu, Y., Liu, W., Ma, J., Lü, N., Zhang, C., & Zhang, C. (2022) · OncoImmunology · doi:10.1080/2162402x.2022.2054105 · Cited by 97
MITA/STING: A central and multifaceted mediator in innate immune response
Ran, Y., Shu, H., & Wang, Y. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.05.003 · Cited by 96
“In light of these observations, it has also been reported that translocon-mediated RIG-I redistribution from the cytosol to MAM is essential for downstream innate immune signaling [68].”
InfluentialChicken STING Mediates Activation of the IFN Gene Independently of the RIG-I Gene
Cheng, Y., Sun, Y., Wang, H., Yan, Y., Ding, C., & Sun, J. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500638 · Cited by 93
“poly(I:C), which is sensed by MDA5 (21, 42).”
BackgroundThe mechanism of STING autoinhibition and activation
Liu, S., Yang, B., Hou, Y., Cui, K., Yang, X., Li, X., Chen, L., Liu, S., Zhang, Z., Jia, Y., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.03.029 · Cited by 102
Cetinbas, N. M., Monnell, T. E., Soomer-James, J., Shaw, P., Lancaster, K. L., Catcott, K. C., Dolan, M., Mosher, R. E., Routhier, C. A., Chin, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49932-4 · Cited by 100
Interfaces between cellular responses to DNA damage and cancer immunotherapyPreprint
Pilger, D., Seymour, L. W., & Jackson, S. P. (2021) · Genes & Development · doi:10.1101/gad.348314.121 · Cited by 96
“…factor 3 (IRF3) and IκBα transduces the initial stimulusof cytosol- ic DNA into IRF3 and NFκB transcriptional programs, which control the balance between cellular survival and controlled cell death (Fitzgerald et al. 2003; Ishikawa and Barber 2008; Ishikawa et al. 2009; Tanaka andChen 2012).”
BackgroundPrantner, D., Perkins, D. J., & Vogel, S. N. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.763268 · Cited by 95
“We predict that this viral susceptibil- ity in the absence of AMPK would be extrapolated to other viruses that signal directly through STING such as HSV-1 (5), adenovirus (6), HIV (4), and Kaposi’s sarcoma-associated herpesvirus (78).”
BackgroundPseudorabies virus tegument protein UL13 recruits RNF5 to inhibit STING-mediated antiviral immunity
Kong, Z., Yin, H., Wang, F., Liu, Z., Luan, X., Sun, L., Liu, W., & Shang, Y. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010544 · Cited by 99
Diner, B. A., Lum, K. K., Javitt, A., & Cristea, I. M. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.047068 · Cited by 93
“Upon binding to their viral cognate ligand, these cellular receptors initiate intracellular immune signaling cascades, culminating in the production and secretion of cytokines, such as type I interferons (IFNs)(1) (1).”
Background
Metadata
- Authors
- Ishikawa, H., Ma, Z., & Barber, G. N.
- Affiliations
- University of Miami (US)
- Corresponding author
- Barber, Glen N.
- Venue
- Nature
- Published
- 2009-09-23
- Volume
- 461
- Issue
- 7265
- Pages
- 788-792
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
- 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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