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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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Radiotherapy, immunity, and immune checkpoint inhibitors
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“Upon binding of cGAMP, STING undergoes conformational changes that trigger its trafficking from the ER to the Golgi to perinuclear endosomes (6).”
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Species‐specific detection of the antiviral small‐molecule compound CMA by STING
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“STING-deficient cells show a profound defect in sensing DNA viruses, and also synthetic DNA ligands are strongly blunted in their capacity to induce pro-inflammatory gene expression in STING-deficient cells (Ishikawa et al , 2009).”
NF-κB activation enhances STING signaling by altering microtubule-mediated STING trafficking
Zhang, L., Wei, X., Wang, Z., Liu, P., Hou, Y., Xu, Y., Su, H., Koci, M. D., Yin, H., & Zhang, C. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112185 · Cited by 199
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BackgroundResultDNA Damage Response and Immune Defense: Links and Mechanisms
Nakad, R., & Schumacher, B. (2016) · Frontiers in Genetics · doi:10.3389/fgene.2016.00147 · Cited by 207
“Activation of TBK-1/IRF-3 signaling axis upon cytosolic DNA sensing is mediated by the stimulator of IFN genes (STING), a transmembrane protein acting as a signaling adaptor (Ishikawa et al., 2009).”
BackgroundThe therapeutic significance of mutational signatures from DNA repair deficiency in cancer
Ma, J., Setton, J. S., Lee, N. Y., Riaz, N., & Powell, S. N. (2018) · Nature Communications · doi:10.1038/s41467-018-05228-y · Cited by 203
BRCA2 abrogation triggers innate immune responses potentiated by treatment with PARP inhibitors
Reisländer, T., Lombardi, E. P., Groelly, F. J., Miar, A., Porru, M., Vito, S. D., Wright, B., Lockstone, H. E., Biroccio, A., Harris, A. L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11048-5 · Cited by 197
Vila, I. K., Chamma, H., Steer, A., Saccas, M., Taffoni, C., Turtoi, E., Reinert, L. S., Hussain, S., Marines, J., Jin, L., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.007 · Cited by 196
“This signaling pathway triggers the production of inflammatory cytokines and type I Interferons (IFNs) (Ishikawa et al., 2009).”
Ubiquitination in the antiviral immune response
Davis-Gardner, M. E., & Gack, M. U. (2015) · Virology · doi:10.1016/j.virol.2015.02.033 · Cited by 197
“Infection studies in sting-knockout mice demonstrated that STING is essential for innate immune signaling upon recognition of foreign intracellular dsDNA (Ishikawa et al., 2009).”
Cellular Innate Immunity: An Old Game with New Players
Gasteiger, G., D’Osualdo, A., Schubert, D. A., Weber, A. N. R., Bruscia, E. M., & Hartl, D. (2016) · Journal of Innate Immunity · doi:10.1159/000453397 · Cited by 210
Ding, Q., Gaska, J. M., Douam, F., Wei, L., Kim, D., Balev, M., Heller, B. L., & Ploß, A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803406115 · Cited by 200
“NS4B protein of other members of the Flaviviridae family—such as HCV, YFV, and DENV—can block STING function (36, 55).”
BackgroundSTING orchestrates the neuronal inflammatory stress response in multiple sclerosis
Woo, M. S., Mayer, C., Binkle-Ladisch, L., Sonner, J. K., Rosenkranz, S. C., Shaposhnykov, A., Rothammer, N., Tsvilovskyy, V., Lorenz, S., Raich, L., et al. (2024) · Cell · doi:10.1016/j.cell.2024.05.031 · Cited by 197
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Self-citationKalamvoki, M., Du, T., & Roizman, B. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1419338111 · Cited by 187
“Knockout of STING exacerbates the pathogenicity of herpes simplex virus (HSV-1) and of other pathogens in mice (2, 3).”
Pharmacological activation of STING blocks SARS-CoV-2 infection
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Ghaffari, A., Peterson, N. T., Khalaj, K., Vitkin, N., Robinson, A. G., Francis, J., & Koti, M. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0188-5 · Cited by 188
Wang, P., Zhao, W., Zhao, K., Zhang, L., & Gao, C. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1004726 · Cited by 184
“Although the nature of DNA sensors needs further investigation, the adaptor protein STING (also called MPYS, MITA, and ERIS) in DNA sensing pathway are well defined [15]-[17].”
BackgroundSensing and Signaling in Antiviral Innate Immunity
O'Neill, L. A. J., & Bowie, A. (2010) · Current Biology · doi:10.1016/j.cub.2010.01.044 · Cited by 183
“Recent studies in STING-deficient mice confirmed that STING has an essential role in mediating IFN induction in response to exogenous DNA, and vesicular stomatitis virus and herpes simplex virus, and also in promoting cytotoxic T-cell responses to plasmid DNA vaccination [41].”
Brault, M., Olsen, T. M., Martinez, J., Stetson, D. B., & Oberst, A. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701492 · Cited by 195
DNA-stimulated cell death: implications for host defence, inflammatory diseases and cancer
Paludan, S. R., Reinert, L. S., & Hornung, V. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-018-0117-0 · Cited by 187
Intrinsic Self-DNA Triggers Inflammatory Disease Dependent on STING
Ahn, J., Ruiz, P., & Barber, G. N. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401337 · Cited by 193
Self-citationcGAS and Ifi204 Cooperate To Produce Type I IFNs in Response to Francisella Infection
Storek, K. M., Talmor, N., Ohlson, M. B., & Monack, D. M. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402764 · Cited by 188
“other cytosolic bacterial pathogen known to trigger a robust STINGdependent type I IFN response (30, 46).”
BackgroundAfrican swine fever virus evasion of host defences
Dixon, L. K., Islam, M., Nash, R. H., & Reis, A. L. (2019) · Virus Research · doi:10.1016/j.virusres.2019.04.002 · Cited by 190
Sze, A., Belgnaoui, S. M., Olagnier, D. P., Lin, R., Hiscott, J. B., & van Grevenynghe, J. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.09.009 · Cited by 188
“The endoplasmic reticulum resident adaptor STING functions as a DNA sensor for bacterial cyclic GTP (Burdette and Vance, 2013) and mediates detection of viral DNA (Ishikawa and Barber, 2008; Ishikawa et al., 2009; Zhong et al., 2008).”
InfluentialImmunomodulatory and antitumor effects of type I interferons and their application in cancer therapy
Medrano, R. F. V., Hunger, A., Mendonça, S. A., Barbuto, J. A. M., & Strauss, B. E. (2017) · Oncotarget · doi:10.18632/oncotarget.19531 · Cited by 192
“Stimulator of interferon genes (STING) acts in the endoplasmic reticulum and promotes the transcriptional functions of nuclear factor-ĸB (NF-ĸB) and IRF3, thus playing a major role in anti-viral response [94].”
BackgroundTransglutaminase Type 2 Regulates ER-Mitochondria Contact Sites by Interacting with GRP75
D’Eletto, M., Rossin, F., Occhigrossi, L., Farrace, M. G., Faccenda, D., Desai, R., Marchi, S., Refolo, G., Falasca, L., Antonioli, M., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.094 · Cited by 191
“STING was found to fractionate with MAMs and mitochondria fractions and then signals to the TANK binding kinase 1 (TBK1)-interferon regulatory factor-3 (IRF3) axis to upregulate type I interferon production (Ishikawa et al., 2009).”
BackgroundPaijo, J., Döring, M., Spanier, J., Grabski, E., Nooruzzaman, M., Schmidt, T., Witte, G., Messerle, M., Hornung, V., Kaever, V., et al. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005546 · Cited by 194
“Murine macrophages stimulated with HCMVmount IFN-I responses that are dependent on the adaptor protein stimulator of interferon genes (STING) [46,47].”
BackgroundResultPromising Targets for Cancer Immunotherapy: TLRs, RLRs, and STING-Mediated Innate Immune Pathways
Li, K., Qu, S., Chen, X., Wu, Q., & Shi, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020404 · Cited by 186
“STING also can activate NF-κB pathway via TRAF6 (TNF receptor-associated factor 6, E3 ubiquitin protein ligase)-TBK1 pathway [104,105].”
BackgroundThe Reciprocity between Radiotherapy and Cancer Immunotherapy
Wang, Y., Liu, Z.-G., Yuan, H., Deng, W., Li, J., Huang, Y.-H., Kim, B. Y. S., Story, M. D., & Jiang, W. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-2581 · Cited by 184
“The presence of mutant DNA within the cytoplasm results in cyclin GMP-AMP (cGAMP), the product of cyclic GMP-AMP synthase (cGAS), to upregulate the transcription of type I IFN (IFN-I) genes via the STING–NFkB signaling pathway (27, 28).”
BackgroundOld dogs, new trick: classic cancer therapies activate cGAS
Yum, S., Li, M., & Chen, Z. J. (2020) · Cell Research · doi:10.1038/s41422-020-0346-1 · Cited by 184
mtDNA-STING Axis Mediates Microglial Polarization via IRF3/NF-κB Signaling After Ischemic Stroke
Kong, L., Li, W., Chang, E., Wang, W., Shen, N., Xu, X., Wang, X., Zhang, Y., Sun, W., Hu, W., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.860977 · Cited by 191
“The phosphorylated STING recruits and activates IRF3, ultimately, IRF3 enters the nucleus and exerts its function in the type-I interferon responses (10, 47).”
BackgroundHepatitis C virus NS4B blocks the interaction of STING and TBK1 to evade host innate immunity
Ding, Q., Cao, X., Lu, J. L., Huang, B. S., Liu, Y.-J., Kato, N., Shu, H., & Zhong, J. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.019 · Cited by 187
“Recent studies have reported that several flaviviruses, including yellow fever virus [12] and dengue virus [27,28], can target STING/ MITA to suppress the interferon signaling by various mechanisms.”
BackgroundNuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA
Orzalli, M. H., Conwell, S. E., Berrios, C. J., DeCaprio, J. A., & Knipe, D. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316194110 · Cited by 184
“STING is an adaptor in intracellular DNA sensing, and decreased expression of STING greatly inhibits IRF-3 activation and type I IFN induction in response to HSV in different cell types (20, 21) and in our system (15).”
BackgroundFrey, B., Rückert, M., Deloch, L., Rühle, P. F., Derer, A., Fietkau, R., & Gaipl, U. S. (2017) · Immunological Reviews · doi:10.1111/imr.12572 · Cited by 189
Therapeutically Active RIG-I Agonist Induces Immunogenic Tumor Cell Killing in Breast Cancers
Elion, D. L., Jacobson, M. E., Hicks, D. J., Rahman, B., Sanchez, V. M., Ericsson, P. I. G., Fedorova, O., Pyle, A. M., Wilson, J. T., & Cook, R. S. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0730 · Cited by 178
“Similar results have been reported from pre-clinical tumor models and clinical trials in cancers assessing the STING-mediated DNA/viral sensing pathway [19, 20, 23], although STING signaling reportedly may be defective in a variety of cancers [24, 25].”
BackgroundInfluentialRIG‐I detects infection with live Listeria by sensing secreted bacterial nucleic acids
Abdullah, Z., Schlee, M., Roth, S., Mraheil, M. A., Barchet, W., Böttcher, J. P., Hain, T., Geiger, S., Hayakawa, Y., Fritz, J. H., et al. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.274 · Cited by 183
“While a role for STING in DNA-mediated recognition of Listeria infection has been suggested (Ishikawa et al , 2009), our results now identify a so far unappreciated role of STING in recognition of Listeria DNA but not RNA secreted via SecA2 leading to production of IFN b .”
Berger, G., Knelson, E. H., Jimenez-Macias, J. L., Nowicki, M. O., Han, S., Panagioti, E., Lizotte, P. H., Adu-Berchie, K., Stafford, A., Dimitrakakis, N., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2111003119 · Cited by 179
“STING agonists promote potent antitumor immunity in preclinical models (25–27, 41, 42), are considered promising anticancer agents with remarkable preclinical efficacy in some tumor models (21, 22, 24, 43, 44), and are being investigated”
BackgroundThe cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications
Shen, M., Jiang, X., Qiu, P., Oyang, L., Ren, Z., Wang, J., Peng, M., Zhou, Y., Deng, X., & Liao, Q. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01691-5 · Cited by 210
“Given the pivotal role of STING in initiating innate immune responses, STING agonists have been proposed as potential adjuvants for cancer vaccines [61].”
Activation of host pattern recognition receptors by viruses
Brennan, K., & Bowie, A. (2010) · Current Opinion in Microbiology · doi:10.1016/j.mib.2010.05.007 · Cited by 176
STING-dependent translation inhibition restricts RNA virus replication
Franz, K. M., Neidermyer, W. J., Tan, Y., Whelan, S. P. J., & Kagan, J. C. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716937115 · Cited by 183
“For example, compared with wild-type (WT) cells, fibroblasts lacking STING support increased replication of vesicular stomatitis virus (VSV) and dengue virus (11, 12, 16, 17).”
BackgroundMethodResultInfluentialChemical Strategies to Boost Cancer Vaccines
Li, W., & Li, Y. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00833 · Cited by 175
Crosstalk between cGAS–STING signaling and cell death
Murthy, A. M. V., Robinson, N., & Kumar, S. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00624-8 · Cited by 178
“The extrinsic pathway is initiated by binding of ‘death ligands’ such as TNF, FASL, TRAIL, to TNF superfamily receptors such as TNF receptor 1 (TNFR1), FAS, death receptor 4/5, respectively, to recruit cytoplasmic adapter proteins such as Fas-associated death domain or TNF-associated death domain.”
BackgroundInfluentialSuppression of systemic autoimmunity by the innate immune adaptor STING
Sharma, S., Campbell, A. M., Chan, J., Schattgen, S., Orlowski, G. M., Nayar, R., Huyler, A. H., Nündel, K., Mohan, C., Berg, L. J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1420217112 · Cited by 172
“Although an increase in proinflammatory cytokines in response to apoptotic cells and TLR9 and TLR3 ligands has been noted previously in STING macrophages by other investigators (33, 35), the significance of this dysregulation of TLR signaling was not addressed further or extended to other TLRs.”
BackgroundImpact of intracellular innate immune receptors on immunometabolism
Chou, W.-C., Rampanelli, E., Li, X., & Ting, J. P. ‐. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00780-y · Cited by 173
Mathur, V., Burai, R., Vest, R. T., Bonanno, L. N., Lehallier, B., Zardeneta, M. E., Mistry, K. N., Do, D., Marsh, S. E., Abud, E. M., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.11.032 · Cited by 175
Dai, P., Wang, W., Cao, H., Avogadri, F., Dai, L., Drexler, I., Joyce, J. A., Li, X.-D., Chen, Z. J., Merghoub, T., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1003989 · Cited by 175
“STING is also important for the development of CD8 T cell responses after vaccination with vaccinia virus expressing ovalbumin [50].”
BackgroundSTING Pathway Activation Stimulates Potent Immunity against Acute Myeloid Leukemia
Curran, E. K., Chen, X., Corrales, L. P., Kline, D. E., Dubensky, T. W., Duttagupta, P. A., Kortylewski, M., & Kline, J. P. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.023 · Cited by 171
STING signaling and host defense against microbial infection
Ahn, J., & Barber, G. N. (2019) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0333-0 · Cited by 180
Self-citationUnterholzner, L., Sumner, R. P., Baran, M., Ren, H., Mansur, D. S., Bourke, N. M., Randow, F., Smith, G. L., & Bowie, A. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002247 · Cited by 176
Interferon-independent STING signaling promotes resistance to HSV-1 in vivo
Yamashiro, L. H., Wilson, S. C., Morrison, H. M., Karalis, V., Chung, J.-Y., Chen, K. J., Bateup, H. S., SZPARA, M. L., Lee, A. Y., Cox, J. S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17156-x · Cited by 176
Strategies for the development of metalloimmunotherapies
Sun, X., Zhou, X., Shi, X., Abed, O. A., An, X., Lei, Y. L., & Moon, J. J. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01221-7 · Cited by 199
“The cytosolic surveillance mechanism of DNA can induce the production of type I IFN (IFN-I) via the activation of STING 54 .”
Similarities and interplay between senescent cells and macrophages
Behmoaras, J., & Gil, J. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202010162 · Cited by 158
“Stimulator of interferon genes is an ER-associated sensor expressed by monocytes/macrophages that regulates nuclear factor–κB (NF-κB) and IRF3-dependent cytokine production (Ishikawa and Barber, 2008; Ishikawa et al., 2009).”
BackgroundCell biology and immunology of Listeria monocytogenes infections: novel insights
Stavru, F., Archambaud, C., & Cossart, P. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00993.x · Cited by 172
“The role of RIG-I in recognition of nucleic acid to induce type I IFNs has been investigated in detail (210, 211).”
BackgroundInterferon-Regulatory Factors Determine Macrophage Phenotype Polarization
Günthner, R., & Anders, H. (2013) · Mediators of Inflammation · doi:10.1155/2013/731023 · Cited by 172
“Additional cytoplasmic DNA recognition receptors use the STING pathway to activate IRF-3 [56].”
BackgroundFang, R., Jiang, Q., Guan, Y., Gao, P., Zhang, R., Zhao, Z., & Jiang, Z. (2021) · Immunity · doi:10.1016/j.immuni.2021.03.011 · Cited by 167
The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response
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STING-Dependent Signaling Underlies IL-10 Controlled Inflammatory Colitis
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“It has recently been shown that another key innate immune pathway, controlled by an endoplasmic reticulum (ER)-associated protein referred to as STING (stimulator of IFN genes), may also be involved in controlling inflammation (Ishikawa andBarber, 2008; Ishikawa et al., 2009).”
Self-citationPositive Feedback Regulation of Type I IFN Production by the IFN-Inducible DNA Sensor cGAS
Ma, F., Li, B., Liu, S.-Y., Iyer, S. S., Yu, Y., Wu, A., & Cheng, G. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402066 · Cited by 173
“cGAMP binding induces a conformational change of STING, which then recruits the kinases TANK-binding kinase 1 (TBK1) to activate IFN regulatory factor (IRF) 3 and trigger IFN-I production (21, 22).”
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“STING is a cytoplasmic DNA sensor, anchored in the endoplasmic reticulum [4-6].”
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Intracellular Pathogen Detection by RIG-I-Like Receptors
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Importance of Nucleic Acid Recognition in Inflammation and Autoimmunity
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Ubiquitination of STING at lysine 224 controls IRF3 activation
Ni, G., Konno, H., & Barber, G. N. (2017) · Science Immunology · doi:10.1126/sciimmunol.aah7119 · Cited by 162
“Activated STING traffics from the ER to endosomal/lysosomal regions to activate IRF3 and NF-B (8, 12, 13).”
BackgroundMethodInfluentialSelf-citationThe cGAS-STING Pathway: A Promising Immunotherapy Target
Ou, L., Zhang, A., Cheng, Y., & Chen, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.795048 · Cited by 166
The balance of STING signaling orchestrates immunity in cancer
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“However, work by Ishikawa et al. 5 succeeding the discovery of STING concluded that IFNβ activation through STING involves the sensing of double-stranded DNA fragments independently of the already described DNA sensor, Toll-like receptor 9 (TLR9).”
García-Belmonte, R., Pérez-Núñez, D., Pittau, M., Richt, J. A., & Revilla, Y. (2019) · Journal of Virology · doi:10.1128/jvi.02298-18 · Cited by 160
“It is remarkable that the activation of STING, after phosphorylation and dimerization, involves trafficking from the ER through the Golgi compartment to perinuclear punctuated structures, called microsomes (33, 34, 63).”
BackgroundExtrachromosomal telomere repeat DNA is linked to ALT development via cGAS-STING DNA sensing pathway
Chen, Y., Shen, Y., Hsia, H.-Y., Tiang, Y. P., Sung, T.-L., & Chen, L. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3498 · Cited by 168
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From periphery to center stage: 50 years of advancements in innate immunity
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“The stimulator of IFN genes (STING) receptor plays a critical role in Toll-like receptor–independent detection of pathogenassociated molecular patterns and type 1 IFN production in the induction of innate immunity (1, 2).”
BackgroundInnate Immune Response to Cytoplasmic DNA: Mechanisms and Diseases
Hu, M., & Shu, H. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-070119-115052 · Cited by 160
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“[56] The TBK1/IRF3 signaling pathway often counteracts the NFκB pathway, which is responsible for increased proinflammatory cytokine production, such as that of IL-6 and TNF-α.”
BackgroundNew developments in the induction and antiviral effectors of type I interferon
Liu, S.-Y., Sanchez, D. J., & Cheng, G. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.11.003 · Cited by 159
The 6th R of Radiobiology: Reactivation of Anti-Tumor Immune Response
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Molecular basis of mycobacterial survival in macrophages
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“Type I IFNs are also induced through the stimulator of interferon genes (STING) and the adaptor TBK1, which are central in some of these pathways [108, 160].”
BackgroundCordova, A. F., Ritchie, C., Böhnert, V., & Li, L. (2021) · ACS Central Science · doi:10.1021/acscentsci.1c00440 · Cited by 157
“STING then activates TBK1, a kinase, and IRF3, a transcription factor, resulting in the expression of inflammatory cytokines.(8) Of particular interest, the type I interferon (IFN-I) class of cytokines is necessary for cGAMP-mediated activation of T cells and effective anti-tumoral immunity.”
Lysosomes in senescence and aging
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“…cyclic GMP – AMP (cGAMP) synthase (cGAS)/stimulator of interferon genes (STING) innate immune pathway (Ishikawa & Barber, 2008; Zhong et al , 2008; Ishikawa et al , 2009; Sun et al , 2009) which has a highly conserved function in autophagy upregulation (Fig 2) (Moretti et al , 2017; Gui et al ,…”
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100 years of Bacillus Calmette–Guérin immunotherapy: from cattle to COVID-19
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Mitochondria: An Organelle of Bacterial Origin Controlling Inflammation
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“Once activated, STING translocates from the ER via the Golgi to perinuclear endosomes (24, 25), where it activates IRF3, NF-κB, and subsequent interferons and inflammatory cytokines, such as TNF and IL-6.”
BackgroundType I interferons: diversity of sources, production pathways and effects on immune responses
Swiecki, M. K., & Colonna, M. (2011) · Current Opinion in Virology · doi:10.1016/j.coviro.2011.10.026 · Cited by 162
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Streptococcus pneumoniae DNA Initiates Type I Interferon Signaling in the Respiratory Tract
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“They are reported to interact with the transmembrane protein stimulator of interferon genes (STING), which then increases the production of type I interferons and further drives the adaptive immune response (Ishikawa et al., 2009; Burdette et al., 2011; Shaw et al., 2013).”
Positive feedback regulation of type I interferon by the interferon‐stimulated gene STING
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“Following activation by pathogenic DNAs or its upstream DNA sensors, STING translocates with TANK-binding kinase 1 (TBK1) to perinuclear endosomes, leading to the activation of interferon regulatory factors (IRFs) and NF-jB, which triggers the expression of type I interferon (IFN-I) and other immune response genes [1,…”
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“Genetic studies demonstrate that MITA but not RIG-I and VISA is essential in type I IFN induction triggered by cytosolic synthetic DNA and DNA virus (13, 25).”
BackgroundIracheta‐Vellve, A., Petrasek, J., Gyöngyösi, B., Satishchandran, A., Lowe, P., Kodys, K., Catalano, D., Calenda, C. D., Kurt‐Jones, E. A., Fitzgerald, K. A., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.736991 · Cited by 151
cGAS and STING: At the intersection of DNA and RNA virus-sensing networks
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“The nonstructural protein NS4B of yellow fever virus (YFV) was the first reported viral protein that interacts and inhibits STING, although the mechanism is unclear [8].”
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Antagonism of the STING Pathway via Activation of the AIM2 Inflammasome by Intracellular DNA
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“Activated STING translocates to and aggregates in the perinuclear region, forming specks (31).”
BackgroundMucosal vaccine adjuvants update
Rhee, J. H., Lee, S. E., & Kim, S. Y. (2012) · Clinical and Experimental Vaccine Research · doi:10.7774/cevr.2012.1.1.50 · Cited by 151
“The addition of genes coding for specific chemokines, e.g., the CCR7 ligands which are involved in directing DC to the T cell areas of secondary lymphoid organs, to a herpes simplex virus 2 DNA plasmid vaccine has stimulated the immune responses in mice following both nasal and intragastric vaccination [105].”
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DNA sensor cGAS-mediated immune recognition
Xia, P., Wang, S., Gao, P., Gao, G., & Fan, Z. (2016) · Protein & Cell · doi:10.1007/s13238-016-0320-3 · Cited by 154
“STING deficient cells fail to produce type I interferons post cytoplasmic DNA stimulation (Ishikawa and Barber, 2008) and STING knockout mice are extremely susceptible to herpes simplex virus 1 infection (Ishikawa et al., 2009).”
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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