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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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“Previous data have shown that phosphorylation of STING occurs after trafficking, typically to negatively regulate STING activity (21, 29).”
BackgroundSelf-citationSTING licensing of type I dendritic cells potentiates antitumor immunity
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BackgroundThe Mosaic Genome of Indigenous African Cattle as a Unique Genetic Resource for African Pastoralism
Kim, K., Kwon, T., Dessie, T., Yoo, D., Mwai, O. A., Jang, J., Sung, S., Lee, S., Salim, B., Jung, J., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0694-2 · Cited by 140
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Roth, S., Rottach, A., Lotz-Havla, A. S., Laux, V., Muschaweckh, A., Gersting, S. W., Muntau, A. C., Hopfner, K., Jin, L., Vanness, K., et al. (2014) · Nature Immunology · doi:10.1038/ni.2888 · Cited by 147
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“The latter was suggested to be related to STING(AbeandMatsuura, 2010)becausebaculovirus-induced IFN-α/β production was impaired in STING-deficient MEFs (Ishikawa et al., 2009), yet IFN-α/β stimulationwas found to be independent of other cytoplasmic RNA detectors such as RIG-I and MDA5 (Abe et al.”
BackgroundSelf-DNA, STING-dependent signaling and the origins of autoinflammatory disease
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Self-citationUbiquitin enzymes in the regulation of immune responses
Ebner, P., Versteeg, G. A., & Ikeda, F. (2017) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2017.1325829 · Cited by 143
“…critical role for this pathway in pathogen defense, STING-deficient mice have increased susceptibility to DNA viruses such as herpes simplex virus (Ishikawa et al. 2009), and cells from these mice fail to induce an interferon response upon infection with this virus or the intra-cellular bacterium…”
BackgroundSTING, DCs and the link between innate and adaptive tumor immunity
Vatner, R. E., & Janssen, E. M. (2017) · Molecular Immunology · doi:10.1016/j.molimm.2017.12.001 · Cited by 139
“: Recently, STING has been identified as an important regulator of immunity by mediating type I IFN production in response to cytosolic DNA (Burdette and Vance, 2013; Ishikawa et al., 2009).”
BackgroundInnate Sensing of DNA Virus Genomes
Ma, Z., Ni, G., & Damania, B. (2018) · Annual Review of Virology · doi:10.1146/annurev-virology-092917-043244 · Cited by 140
“Evidence has shown that STING can bind to transfected ssDNA in cells or in vitro and is responsible for ssDNAtriggered type I IFN production (30, 33, 34).”
BackgroundSelf-citationSTING-Dependent Type I IFN Production Inhibits Cell-Mediated Immunity to Listeria monocytogenes
Archer, K. A., Durack, J., & Portnoy, D. A. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1003861 · Cited by 137
“Direct binding of CDNs to STING activates a downstream signaling cascade involving TBK1 and IRF3 [11,12,13].”
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“Furthermore, immunogenicity Ingolotti, Kawalekar, Shedlock, Muthumani & Weiner www.expert-reviews.com 753 Review of plasmid DNA may be due in part to the production of type 1 IFNs following the cellular detection of intracellular dsDNA by signaling molecules including STING and TBK1, which complex and traffic to endos…”
Strategies Used by Bacteria to Grow in Macrophages
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“For example, DNA from M. tuberculosis , PrgJ from S. enterica , and the fl agellum of L. pneumophila are recognized by the host cytosolic sensing machinery. toxins and might constitute a host protection or de-toxi fi cation mechanism (300, 301).”
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cGAS‐cGAMP‐STING: The three musketeers of cytosolic DNA sensing and signaling
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“Many DNA viruses have been reported to trigger cGAScGAMP-STING mediated antiviral responses upon recognition of viral DNA by cGAS, including herpes simplex virus 1 (HSV1) (59,82), murine gamma-herpesvirus 68 (MHV68) (52), Kaposi’s sarcoma-associated herpesvirus (KSHV) (103), vaccinia virus (VACV) (59), adenovirus (104…”
BackgroundMethodSENP7 Potentiates cGAS Activation by Relieving SUMO-Mediated Inhibition of Cytosolic DNA Sensing
Cui, Y., Yu, H., Zheng, X., Peng, R., Wang, Q., Zhou, Y., Wang, R., Wang, J., Qu, B., Shen, N., et al. (2017) · PLoS Pathogens · doi:10.1371/journal.ppat.1006156 · Cited by 138
“As a second messenger, cGAMP directly binds to and activates the ER-resident stimulator of interferon genes (STING), a converging adaptor for all known cytosolic DNA sensors [19].”
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“First identified by expression cloning, STING was shown to activate both NF-κB and IRF3 transcription pathways to induce expression of IFN-I and exert a potent antiviral state following expression (Ishikawa, Ma, & Barber, 2009).”
BackgroundInfluentialSTING Mediates Neuronal Innate Immune Response Following Japanese Encephalitis Virus Infection
Nazmi, A., Mukhopadhyay, R., Dutta, K., & Basu, A. (2012) · Scientific Reports · doi:10.1038/srep00347 · Cited by 129
“STING −/− animals were also found to be more susceptible to vesicular stomatitis virus infection which is indicative of impaired immunit”
The TRIMendous Role of TRIMs in Virus–Host Interactions
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“The listed double-strand (ds) DNA receptors activate the adaptor molecule stimulator of IFN genes (STING) at the endoplasmic reticulum (ER) [117] [118] [119] [120] [121] .”
BackgroundZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response
Lian, H., Wei, J., Zang, R., Ye, W., Yang, Q., Zhang, X., Chen, Y.-D., Fu, Y.-Z., Hu, M., Lei, C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05559-w · Cited by 132
ABCC1 transporter exports the immunostimulatory cyclic dinucleotide cGAMP
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“…that binds to double-stranded DNA and catalyzes the formation of cyclic GMP-AMP (cGAMP; Sun et al., 2013; Wu et al., 2013), a diffusible cyclic dinucleotide (CDN) that activates the adaptor protein stimulator of interferon genes (STING) on the endoplasmic reticulum (Ishikawa et al., 2009).”
HSV-2: in pursuit of a vaccine
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“), which has been shown in a number of studies to facilitate TBK1-mediated IFN-β induction”
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Yin, Q., Fu, T., Li, J., & Wu, H. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112258 · Cited by 135
cGAS-STING Signaling Regulates Initial Innate Control of Cytomegalovirus Infection
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“Recent studies using transfected dsDNA and HSV-1 (an alphaherpesvirus) have uncovered two important new players in cytosolic DNA sensing, cGAS and STING (19, 34).”
BackgroundInnate immune mediators in cancer: between defense and resistance
Berraondo, P., Minute, L., Ajona, D., Corrales, L. P., Melero, I., & Pı́o, R. (2016) · Immunological Reviews · doi:10.1111/imr.12464 · Cited by 134
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“Activated STING relocalizes to perinuclear vesicles to initiate TBK1 kinase-dependent phosphorylation of the transcription factor IRF3 and expression of type I interferons (Ishikawa et al., 2009; Tanaka and Chen, 2012).”
BackgroundSubversion of Host Recognition and Defense Systems by Francisella spp
Jones, C. L., Napier, B. A., Sampson, T. R., Llewellyn, A. C., Schroeder, M. R., & Weiss, D. S. (2012) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.05027-11 · Cited by 135
“STING is known to induce type I IFN production in response to cytosolic double-stranded DNA (dsDNA) derived from transfected plasmids, viruses, and some bacteria (107).”
BackgroundMetabolic signaling functions of ER–mitochondria contact sites: role in metabolic diseases
Tubbs, E., & Rieusset, J. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0189 · Cited by 130
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“STING, an ER protein shown to be required for intracellular DNA-mediated, type I interferon-dependent innate immunity (Ishikawa et al., 2009), is also required for the recognition of c-di-GMP and another bacterial second messenger, c-di-AMP (Sauer et al., 2011).”
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“Viral infection or stimulation by dsDNA activates STING by relocating it from the ER to the Golgi and causing its assembly into punctate structures, where STING associates with TBK1 [41].”
The Emerging Roles of STING in Bacterial Infections
Marinho, F. V., Benmerzoug, S., Oliveira, S. C., Ryffel, B., & Quesniaux, V. F. J. (2017) · Trends in Microbiology · doi:10.1016/j.tim.2017.05.008 · Cited by 127
“monocytogenes both in vitro [2, 16, 84] and in vivo [85].”
BackgroundIntracellular bacteria engage a STING–TBK1–MVB12b pathway to enable paracrine cGAS–STING signalling
Nandakumar, R., Tschismarov, R., Meissner, F., Prabakaran, T., Krissanaprasit, A., Farahani, E., Zhang, B., Assil, S., Martin, A., Bertrams, W., et al. (2019) · Nature Microbiology · doi:10.1038/s41564-019-0367-z · Cited by 131
Innate immunity signalling and membrane trafficking
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STING-associated lung disease in mice relies on T cells but not type I interferon
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Modulation of tumor microenvironment for immunotherapy: focus on nanomaterial-based strategies
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“DNA-mediated IFN-dependent innate immunity [161], demonstrating the potential of STING-mediated cancer immunotherapy.”
BackgroundThe STING pathway and regulation of innate immune signaling in response to DNA pathogens
Ishikawa, H., & Barber, G. N. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0605-2 · Cited by 131
Self-citationTRIM56 Is a Virus- and Interferon-Inducible E3 Ubiquitin Ligase That Restricts Pestivirus Infection
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“, MITA/ERIS/MYPS), an adaptor protein essential 21 for dsDNA induction of IFN (12, 31, 40).”
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Self-citationALK is a therapeutic target for lethal sepsis
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Dual Targeting of Innate and Adaptive Checkpoints on Tumor Cells Limits Immune Evasion
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“DNA can enter the cytosol either through DNA transfection or from bacterial species that access the cytosol likely through inadvertent bacterial lysis (see dsDNA) (103).”
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“Growing evidence also supports the existence of multiple cytosolic and nuclear DNA-sensing receptors, which lead to activation of STING and TBK-1-dependent phosphorylation of IRF3 and transcription of type I IFN genes (11, 12).”
BackgroundHuman DEAD Box Helicase 3 Couples IκB Kinase ε to Interferon Regulatory Factor 3 Activation
Gu, L., Fullam, A., Brennan, R., & Schröder, M. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01603-12 · Cited by 125
“downstream of cytosolic DNA receptors (40).”
Activation and Regulation of DNA-Driven Immune Responses
Paludan, S. R. (2015) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00061-14 · Cited by 128
“The first demonstration of the role of the intracellular DNA sensing pathway in host defense was a report of STING-deficient mice being highly susceptible to intravenous HSV-1 infection, with accelerated mortality and elevated viral loads in the brain (80).”
BackgroundFeng, H., Zhang, Y.-B., Zhang, Q.-M., Li, Z., Zhang, Q.-Y., & Gui, J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1402415 · Cited by 123
Targeting Cytosolic Nucleic Acid-Sensing Pathways for Cancer Immunotherapies
Iurescia, S., Fioretti, D. P., & Rinaldi, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00711 · Cited by 124
“A phosphorylation cascade allows signal transmission leading to activation of interferon regulatory factor (IRF) 3 and nuclear factor κB (NF-κB) that translocate into the nucleus to drive transcription of type-I interferons (IFNs), interferon-stimulated genes (ISGs), proinflammatory cytokines and chemokines (5, 6).”
BackgroundReinert, L. S., Rashidi, A. S., Tran, D. N., Katzilieris-Petras, G., Hvidt, A. K., Gohr, M., Fruhwürth, S., Bodda, C., Thomsen, M. K., Vendelbo, M. H., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci136824 · Cited by 118
“cGAS-STING pathway is essential for control of HSV-1 infection in mouse models for HSV-1 brain 28 infection (25-27).”
BackgroundMcFarlane, S., Aitken, J. D., Sutherland, J. S., Nicholl, M. J., Preston, V. G., & Preston, C. M. (2011) · Journal of Virology · doi:10.1128/jvi.02435-10 · Cited by 123
“DAI mediates this effect through the activation of IRF3, but it is possible that intermediate molecules in the cascade, such as the adaptor STING/MITA (27, 77), also activate autophagy.”
BackgroundAutophagy and innate immunity: Triggering, targeting and tuning
Sumpter, R., & Levine, B. (2010) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2010.04.003 · Cited by 129
Replication Stress, DNA Damage, Inflammatory Cytokines and Innate Immune Response
Ragu, S., Matos-Rodrigues, G. E., & López, B. S. (2020) · Genes · doi:10.3390/genes11040409 · Cited by 131
“Phosphorylated STING then binds the transcription factor Interferon Regulatory Factor 3 (IRF3), which is subsequently phosphorylated by TBK1 [47,48,50,51].”
BackgroundCadmium activates the innate immune system through the AIM2 inflammasome
Zhao, L., Liao, M., Li, L., Chen, L., Zhang, T., & Li, R. (2024) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2024.111122 · Cited by 130
Significance of optineurin mutations in glaucoma and other diseases
Minegishi, Y., Nakayama, M., Iejima, D., Kawase, K., & Iwata, T. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.08.002 · Cited by 126
Selection of DNA-Encoded Libraries to Protein Targets within and on Living Cells
Cai, B., Kim, D., Akhand, S. S., Sun, Y., Cassell, R. J., Alpsoy, A., Dykhuizen, E. C., van Rijn, R. M., Wendt, M. K., & Krusemark, C. J. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b08085 · Cited by 121
Regulation of RIG-I-like receptor signaling by host and viral proteins
Chiang, J. J., Davis-Gardner, M. E., & Gack, M. U. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.06.005 · Cited by 122
“Over the past few years, a growing number of substrates for Lys63-linked ubiquitination have been described that are involved in diverse processes,including DNA repair, protein transport, translation and innate immune signaling [61].”
InfluentialPRRs are watching you: Localization of innate sensing and signaling regulators
Chow, J., Franz, K. M., & Kagan, J. C. (2015) · Virology · doi:10.1016/j.virol.2015.02.051 · Cited by 128
“Stimulator of IFN genes (STING) is an ER-localized protein that coordinates the typeI IFN response to viral DNA (Ishikawa et al., 2009; Ishikawa and Barber 2008).”
BackgroundYanai, H., Chiba, S., Hangai, S., Kometani, K., Inoue, A., Kimura, Y., Abe, T., Kiyonari, H., Nishio, J., Taguchi‐Atarashi, N., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1803936115 · Cited by 122
“A similar observation was made in MEFs infected by HSV-1 and Listeria monocytogenes, which are activated mainly by cytosolic DNA sensors (2, 12, 23, 24) (Fig.”
ResultViral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion
Xu, G., Liu, C., Zhou, S. D., Li, Q., Feng, Y., Sun, P., Feng, H., Gao, Y., Zhu, J., Luo, X., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.05.002 · Cited by 125
Biochemistry, Cell Biology, and Pathophysiology of the Innate Immune cGAS–cGAMP–STING Pathway
Ritchie, C., Carozza, J. A., & Li, L. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-040320-101629 · Cited by 123
Sensing of M ycobacterium tuberculosis and consequences to both host and bacillus
Stamm, C. E., Collins, A. C., & Shiloh, M. U. (2015) · Immunological Reviews · doi:10.1111/imr.12263 · Cited by 131
“Phosphorylated IRF3 then dimerizes and translocates to the nucleus where it induces IFN-b production (162, 163).”
BackgroundSen, T., Corte, C. M. D., Milutinovic, S., Cardnell, R. J., Diao, L., Ramkumar, K., Gay, C. M., Stewart, C. A., Fan, Y.-H., Shen, L., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.08.009 · Cited by 122
Mitochondrial Quality Control and Restraining Innate Immunity
Moehlman, A. T., & Youle, R. J. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-021820-101354 · Cited by 125
The role of cGAS-STING signalling in liver diseases
Chen, R., Du, J., Zhu, H., & Ling, Q. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100324 · Cited by 131
“translocated to the nucleus where it initiates transcription of IFN-I.(34,35) STING also recruits IjB kinase (IKK), which phosphorylates IjBa and induces translocation of NF-jB to the nucleus, where it transcribes a plethora of cytokines such as”
BackgroundCD 4+ T‐cell help amplifies innate signals for primary CD 8+ T‐cell immunity
Bedoui, S., Heath, W. R., & Mueller, S. N. (2016) · Immunological Reviews · doi:10.1111/imr.12426 · Cited by 128
“The original report of enhanced susceptibility of STING-deficient mice to HSV encephalitis and lethality was most likely related to infections with a higher viral dose through a systemic , rather than peripheral route of infection, in which even 25% of wild type mice succumb ed to HSV encephalitis (54).”
BackgroundHuman Cytomegalovirus Protein UL31 Inhibits DNA Sensing of cGAS to Mediate Immune Evasion
Huang, Z.-F., Zou, H.-M., Liao, B.-W., Zhang, H.-Y., Yang, Y., Fu, Y.-Z., Wang, S., Luo, M., & Wang, Y. (2018) · Cell Host & Microbe · doi:10.1016/j.chom.2018.05.007 · Cited by 127
Guo, H., Gilley, R. P., Fisher, A. D., Lane, R. K., Landsteiner, V. J., Ragan, K. B., Dovey, C. M., Carette, J. E., Upton, J. W., Mocarski, E. S., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0868-3 · Cited by 121
Hu, M., He, W.-R., Gao, P., Yang, Q., He, K. F., Cao, L.-B., Li, S., Feng, Y., & Shu, H. (2019) · Cell Research · doi:10.1038/s41422-018-0136-1 · Cited by 121
Tkach, M., Thalmensi, J., Timperi, E., Gueguen, P., Névo, N., Grisard, E., Sirven, P., Cocozza, F., Gouronnec, A., Jaular, L. M., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2107394119 · Cited by 121
Cryo-EM structure of an active bacterial TIR–STING filament complex
Morehouse, B. R., Yip, M. C. J., Keszei, A. F. A., McNamara-Bordewick, N. K., Shao, S., & Kranzusch, P. J. (2022) · Nature · doi:10.1038/s41586-022-04999-1 · Cited by 117
Animal models of herpes simplex virus immunity and pathogenesis
Kollias, C. M., Huneke, R. B., Wigdahl, B. L., & Jennings, S. R. (2014) · Journal of NeuroVirology · doi:10.1007/s13365-014-0302-2 · Cited by 119
“These include Toll-like receptors (TLRs) on cellular plasma membranes (e.g., TLR2), within endosomes (e.g., TLR3 and TLR9), and cytosolic nucleic acid receptors (e.g., DAI, IFI16, and Rig-I) (Conrady et al. 2012; Davey et al. 2010; Ishikawa et al. 2009; Kurt-Jones et al. 2004; Lund et al. 2006).”
BackgroundResistance to HSV-1 infection in the epithelium resides with the novel innate sensor, IFI-16
Conrady, C. D., Zheng, M., Fitzgerald, K. A., Liu, C.-J., & Carr, D. J. J. (2012) · Mucosal Immunology · doi:10.1038/mi.2011.63 · Cited by 118
Both STING and MAVS Fish Orthologs Contribute to the Induction of Interferon Mediated by RIG-I
Biacchesi, S., Mérour, E., Lamoureux, A., Bernard, J., & Brémont, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047737 · Cited by 123
Novel Strategies to Improve DNA Vaccine Immunogenicity
Coban, C., Kobiyama, K., Aoshi, T., Takeshita, F., Horii, T., Akira, S., & Ishii, K. J. (2011) · Current Gene Therapy · doi:10.2174/156652311798192815 · Cited by 117
Targeting Innate Immunity in Cancer Therapy
Rameshbabu, S., Labadie, B. W., Argulian, A., & Patnaik, A. (2021) · Vaccines · doi:10.3390/vaccines9020138 · Cited by 121
Lee, S. J., Yang, H., Kim, W. R., Lee, Y. S., Lee, W. S., Kong, S. J., Lee, H. J., Kim, J. H., Cheon, J., Kang, B., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002195 · Cited by 118
Molecular Basis of DNA Recognition in the Immune System
Atianand, M., & Fitzgerald, K. A. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203162 · Cited by 125
“STING deficiency in macrophages or DCs leads to a markedly impaired type I IFN response to BDNA and immunostimulatory DNA or to infection with DNA viruses, including HSV-1, human CMV, and vaccinia virus (42, 45).”
BackgroundLee, M. N., Roy, M., Ong, S., Mertins, P., Villani, A., Li, W., Dotiwala, F., Sen, J., Doench, J. G., Orzalli, M. H., et al. (2012) · Nature Immunology · doi:10.1038/ni.2509 · Cited by 124
Systemic DNA damage responses in aging and diseases
Ribezzo, F., Shiloh, Y., & Schumacher, B. (2016) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.12.005 · Cited by 116
“In order to activate the TBK1-IRF3 pathway, stimulator of IFN genes (STING) is necessary to accompany TBK1 to the endosomal compartments for the activation of IRF3/IRF7 [120,121].”
Biolatti, M., Dell’Oste, V., Pautasso, S., Gugliesi, F., von Einem, J., Krapp, C., Jakobsen, M. R., Borgogna, C., Gariglio, M., Andrea, M. D., et al. (2017) · Journal of Virology · doi:10.1128/jvi.01774-17 · Cited by 122
“Finally, VP16, an abundant 65-kDa HSV-1 virion phosphoprotein, has been shown to inhibit IRF3 from recruiting its coactivator CREB-103 binding protein, thereby blocking its transactivation activity (35).”
InfluentialChoi, H. J., Park, A., Kang, S., Lee, E., Lee, T. A., Ra, E. A., Lee, J., Lee, S., & Park, B. (2018) · Nature Communications · doi:10.1038/s41467-017-02624-8 · Cited by 116
Konno, H., Chinn, I. K., Hong, D. N., Orange, J. S., Lupski, J. R., Mendoza, A., Pedroza, L. A., & Barber, G. N. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.115 · Cited by 118
“…apparatus, with TANK-binding kinase 1 (TBK1) to activate the transcription factors IRF3 and nuclear factor kB (NF-kB), which stimulate the production of type I interferon (IFN) and pro-inflammatory cytokines, which facilitate adaptive immunity (Ishikawa and Barber, 2008; Ishikawa et al., 2009).”
InfluentialSelf-citationPharmacological Modulation of the STING Pathway for Cancer Immunotherapy
Berger, G., Marloye, M., & Lawler, S. E. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.02.007 · Cited by 117
“The produced endogenous cGAMP ligand in turn binds the STING dimer [43], inducing conformational changes and the trafficking of the protein into perinuclear Golgi vesicles [44].”
Background4-Octyl itaconate restricts STING activation by blocking its palmitoylation
Su, C., Cheng, T., Huang, J., Zhang, T., & Yin, H. H. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113040 · Cited by 116
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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