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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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“The involvement of STING (an endoplasmic reticulum (ER) adaptor) in the cGAS signaling pathway-dependent type 1 IFN generation in response to the cytosolic DNA recognition was determined in 2008 and 2009 by the same research group (18, 19).”
MethodArwert, E. N., Milford, E. L., Rullan, A., Derzsi, S., Hooper, S., Kato, T., Mansfield, D., Melcher, A., Harrington, K. J., & Sahai, E. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0527-7 · Cited by 90
Type I IFN activating type I dendritic cells for antitumor immunity
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“Upon encountering double-stranded DNA, cGAS catalyzes the synthesis of cyclic-di-GMP-AMP, which in turn binds the adapter protein STING on the endoplasmic reticulum and promotes TBK1-dependent IRF3 andNF-kB activation to further produce type I IFNs, proinflammatory cytokines, and chemokines to initiate adaptive antitu…”
BackgroundCrosstalk between Mycobacterium tuberculosis and the host cell
Dey, B., & Bishai, W. R. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.09.002 · Cited by 92
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“The cytoplasmic localization of IFI16-b prompted us to investigate its Notably, the discrete punctate staining pattern of STING in the cyto-plasm of these cells was compatible with the notion that aggregate formation was required for its activation [44 – 46].”
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Autophagy and Protein Secretion
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“This pathway has two major components: cGAMP synthase (cGAS) and Stimulator of interferon genes (STING) (1, 2).”
BackgroundDissection of a type I interferon pathway in controlling bacterial intracellular infection in mice
Lippmann, J., Müller, H. C., Naujoks, J., Tabeling, C., Shin, S., Witzenrath, M., Hellwig, K., Kirschning, C. J., Taylor, G. A., Barchet, W., et al. (2011) · Cellular Microbiology · doi:10.1111/j.1462-5822.2011.01646.x · Cited by 94
“In contrast, knock-down of STING partially reduced the type I IFN response in Legionella -infected cells (Fig.”
BackgroundInfluentialSun, C., Schattgen, S., Pisitkun, P., Jørgensen, J., Hilterbrand, A. T., Wang, L. J., West, J. A., Hansen, K., Horan, K., Jakobsen, M. R., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402495 · Cited by 85
“Advances in the field of innate immunology have revealed important roles for the innate immune system in host control of herpesvirus infections (2-4).”
InfluentialEvasion of Cytosolic DNA-Stimulated Innate Immune Responses by Herpes Simplex Virus 1
Zheng, C. (2018) · Journal of Virology · doi:10.1128/jvi.00099-17 · Cited by 89
“Recent studies have shown that HSV-1 can evade the DNA-sensor-mediated antiviral responses at the level of both recognition through multiple DNA sensors and innate immune signaling through the STING-TBK1IRF3 or NF- B axis (Fig.”
BackgroundInfluentialDDX24 Negatively Regulates Cytosolic RNA-Mediated Innate Immune Signaling
Ma, Z., Moore, R. H., Xu, X., & Barber, G. N. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003721 · Cited by 89
Self-citationA cGAS-Independent STING/IRF7 Pathway Mediates the Immunogenicity of DNA Vaccines
Suschak, J. J., Wang, S., Fitzgerald, K. A., & Lu, S. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1501836 · Cited by 87
“Furthermore, both molecules have been identified as key regulators of IFN-ab production following DNA virus infection (24, 39).”
BackgroundInfluentialNatural STING Agonist as an “Ideal” Adjuvant for Cutaneous Vaccination
Wang, J., Li, P., & Wu, M. X. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.05.105 · Cited by 88
“MHC IIGFP mice expressing MHC class II molecule infused into enhanced green fluorescent protein (GFP) and STING−/− mice were kindly gifts of Dr. Hidde Ploegh, Massachusetts Institute of Technology and Dr. Glen Barber, University of Miami, respectively (Boes et al, 2002, Ishikawa et al, 2009).”
BackgroundMethodSTING signalling protects against chronic pancreatitis by modulating Th17 response
Zhao, Q., Manohar, M., Wei, Y., Pandol, S. J., & Habtezion, A. (2019) · Gut · doi:10.1136/gutjnl-2018-317098 · Cited by 88
Termination of STING responses is mediated via ESCRT‐dependent degradation
Balka, K. R., Venkatraman, R., Saunders, T. L., Shoppee, A., Pang, E. S., Magill, Z., Homman‐Ludiye, J., Huang, C., Lane, R. M., York, H. M., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022112712 · Cited by 92
“…by disrupting the ADP-ribosylation factor (ARF) GTPases with either the toxin Brefeldin A or a Shigella effector protein inhibits STING signalling, completely blocking STING-driven inflammation (Ishikawa et al, 2009; Konno et al, 2013; Dobbs et al, 2015; Ni et al, 2017; Ogawa et al, 2018).”
BackgroundKemmoku, H., Takahashi, K., Mukai, K., Mori, T., Hirosawa, K. M., Kiku, F., Uchida, Y., Kuchitsu, Y., Nishioka, Y., Sawa, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44317-5 · Cited by 95
Message in a bottle: lessons learned from antagonism of STING signalling during RNA virus infection
Maringer, K., & Fernández-Sesma, A. (2014) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2014.08.004 · Cited by 90
“…via RIG-I, STING interacts with the adapter protein MAVS at the MAM or mitochondria, and after its translocation to perinuclear vesicles, STING then acts as a scaffold for the recruitment of TBK1 and other signalling components required for IRF-3 activation and type I IFN induction [3] [4] [7] [8].”
Type I interferons and endoplasmic reticulum stress in health and disease
(2020) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.10.004 · Cited by 83
“site of physical association between mitochondria and ER (Ishikawa et al., 2009).”
Acute Infection of Viral Pathogens and Their Innate Immune Escape
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RNA viruses and the cGAS-STING pathway: reframing our understanding of innate immune sensing
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TRAF5 Is a Downstream Target of MAVS in Antiviral Innate Immune Signaling
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DNA Degradation and Its DefectsPreprint
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“STING, also called TMEM173, is a transmembrane protein at the endoplasmic reticulum that is essential for the innate immune response against DNA and RNA viruses such as HSV, HIV, and RSV (Ishikawa and Barber 2008; Ishikawa et al. 2009).”
BackgroundZhang, Z.-D., Xiong, T.-C., Yao, S., Wei, M., Chen, M., Lin, D., & Zhong, B. (2020) · Nature Communications · doi:10.1038/s41467-020-19318-3 · Cited by 87
CircPVT1 promotes ER‐positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS
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“STING is located in endoplasmic reticulum and is responsive to exogenous DNA virus infection or endogenous DNA breaks (Ishikawa & Barber, 2008; Ishikawa et al, 2009).”
PRMT1 mediated methylation of cGAS suppresses anti-tumor immunity
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“The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has recently been identified as a pattern recognition receptor (PRR), which functions as a cytosolic double-stranded DNA (dsDNA) sensor during viral or bacterial infection [17,18].”
STING Requires the Adaptor TRIF to Trigger Innate Immune Responses to Microbial Infection
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“STING provides protection against many bacterial and viral infections (Archer et al., 2014; Dey et al., 2015; Hartlova et al., 2015; Ishikawa et al., 2009); for example, STING signaling protects cells and mice from pathogenesis caused by Listeria monocytogenes and herpes simplex virus 1 (HSV-1).”
BackgroundCytosolic nucleic acid sensors and innate immune regulation
Ori, D., Murase, M., & Kawai, T. (2017) · International Reviews of Immunology · doi:10.1080/08830185.2017.1298749 · Cited by 86
“Moreover, STING is also important in certain autoimmune diseases and DNA vaccine adjuvanticity [121, 122].”
BackgroundKnipe, D. M. (2015) · Virology · doi:10.1016/j.virol.2015.02.009 · Cited by 85
“(Ishikawa et al., 2009), an endoplasmic reticulum–localized, transmembrane protein that bridges DNA-sensing mechanisms to down-”
BackgroundLiao, Z., Wan, Q., Su, H., Wu, C., & Su, J. (2017) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2017.05.019 · Cited by 85
Herpes Simplex Virus 1 γ 1 34.5 Protein Inhibits STING Activation That Restricts Viral Replication
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“Furthermore, given that STING critically primes adaptive immunity (37, 38), it is reasonable to postulate that control over STING is advantageous to HSV, likely at multiple levels in vivo.”
BackgroundMahil, S. K., Capon, F., & Barker, J. N. (2014) · Dermatologic Clinics · doi:10.1016/j.det.2014.09.001 · Cited by 85
RIG-I-Mediated STING Upregulation Restricts Herpes Simplex Virus 1 Infection
Liu, Y., Goulet, M.-L., Sze, A., Hadj, S. B., Belgnaoui, S. M., Lababidi, R. R., Zheng, C., Fritz, J. H., Olagnier, D. P., & Lin, R. (2016) · Journal of Virology · doi:10.1128/jvi.00748-16 · Cited by 88
“ings of previous studies, STING is essential for protection against lethal challenge with HSV-1 (18, 61).”
ResultInduction of type I IFNs by intracellular DNA‐sensing pathways
Cavlar, T., Ablasser, A., & Hornung, V. (2012) · Immunology and Cell Biology · doi:10.1038/icb.2012.11 · Cited by 84
IL-26 Confers Proinflammatory Properties to Extracellular DNA
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“STING, expressed in numerous cell types (including myeloid and lymphoid cells) (2, 3), recognizes a wide variety of DNA (4).”
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“The activation of the STING pathway by recognition of cytosolic DNA can induce the production of type I interferons (IFNs) and other cytokines [1,2], and modulation of STING activity has recently become an attractive therapeutic strategy in the field of immunology for the treatment of cancers, autoimmune diseases, and…”
BackgroundSpatially clustered type I interferon responses at injury borderzones
Ninh, V. K., Calcagno, D. M., Yu, J. D., Zhang, B., Taghdiri, N., Sehgal, R., Mesfin, J. M., Chen, C. J., Kalhor, K., Toomu, A., et al. (2024) · Nature · doi:10.1038/s41586-024-07806-1 · Cited by 86
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Innate Antiviral Immune Signaling, Viral Evasion and Modulation by HIV-1
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“However, despite the many DNA sensing mechanisms described above, and while the adaptor STING is essential for the cytoplasmic DNA response [60], no individual DNAsensing PRR appears to be essential for DNA-dependent type I IFN production in all cell types, and this notion is still true after the recent discovery of c…”
BackgroundEffective and lesion-free cutaneous influenza vaccination
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“Upon binding to the sensor, the activation signal is transduced to the adaptor protein STING (35), followed by activation of Type I IFN transcription through a TBK1-IRF3–mediated pathway or by activation of proinflammatory cytokines through NFκB pathway (36).”
BackgroundInfluentialViral evasion of DNA-stimulated innate immune responses
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Nonspecific DNA Binding of cGAS N Terminus Promotes cGAS Activation
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“This causes further recruitment of the transcription factor IRF3 to MITA and its phosphorylation by TBK1 (2, 3).”
BackgroundInfluentialSelf-guarding of MORC3 enables virulence factor-triggered immunity
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Role of released mitochondrial DNA in acute lung injury
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Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles
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S6K-STING interaction regulates cytosolic DNA–mediated activation of the transcription factor IRF3
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STING signaling is a potential immunotherapeutic target in colorectal cancer
Chon, H. J., Kim, H., Noh, J. H., Yang, H., Lee, W. S., Kong, S. J., Lee, S., Lee, Y. S., Kim, W. R., Kim, J. H., et al. (2019) · Journal of Cancer · doi:10.7150/jca.32806 · Cited by 83
“http://www.jcancer.org Background: Stimulator of Interferon Genes (STING) is an innate immune sensor for cytosolic DNA.”
BackgroundInfluentialLin, B., Berard, R. A., Rasheed, A. A., Al‐Adba, B., Kranzusch, P. J., Henderlight, M., Grom, A., Kahle, D., Torreggiani, S., Aue, A. G., et al. (2020) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2020.06.032 · Cited by 87
STING, a promising target for small molecular immune modulator: A review
Liu, Y., Lü, X., Qin, N., Qiao, Y., Xing, S., Liu, W., Feng, F., Liu, Z., & Sun, H. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.113113 · Cited by 80
AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity
Zhang, Q., Liu, S., Zhang, C., Wu, Q., Yu, X., Zhou, R., Meng, F., Wang, A., Zhang, F., Chen, S., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.10.026 · Cited by 85
STING directly recruits WIPI2 for autophagosome formation during STING‐induced autophagy
Wan, W., Qian, C., Wang, Q., Li, J., Zhang, H., Wang, L., Pu, M., Huang, Y., He, Z., Zhou, T., et al. (2023) · The EMBO Journal · doi:10.15252/embj.2022112387 · Cited by 84
“Mice deficient in cGAS-STING signaling are susceptible to lethal infection by DNA viruses (Ishikawa et al, 2009; Li et al, 2013), highlighting the critical role of the cGAS-STING pathway in combating viral infection.”
BackgroundXu, Y., Yuen, P.-W., & Lam, J. K. W. (2014) · Pharmaceutics · doi:10.3390/pharmaceutics6030378 · Cited by 84
“DNA vaccines also interact with cytoplasmic DNA sensors including TANK-binding kinase 1 (TBK1) [24] and stimulator of IFN genes ( STING ) [25], activating TLR-independent pathways and inducing IFN-γ .”
BackgroundAvian oncogenic herpesvirus antagonizes the cGAS-STING DNA-sensing pathway to mediate immune evasion
Li, K., Liu, Y., Xu, Z., Zhang, Y., Luo, D., Gao, Y., Qian, Y., Bao, C., Liu, C., Zhang, Y., et al. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007999 · Cited by 82
“Furthermore, various bacteria have also been reported to promote STING signaling via genomic DNA and secretion of STING-activating cyclic dinucleotides [12, 43].”
BackgroundThe cGAS-STING Pathway: Novel Perspectives in Liver Diseases
Xu, D., Tian, Y., Xia, Q., & Ke, B. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.682736 · Cited by 87
Activation of human STING by a molecular glue-like compound
Li, J., Canham, S. M., Wu, H. J., Hénault, M., Chen, L., Liu, G., Chen, Y., Yu, G. Z., Miller, H., Horn̆ák, V., et al. (2023) · Nature Chemical Biology · doi:10.1038/s41589-023-01434-y · Cited by 84
“Cryo-EM micrographs of STING with both cGAMP and of the high-order oligomer and translocation from the endoplasmic reticulum to the Golgi 12,17–20 .”
Inhibition of TANK Binding Kinase 1 by Herpes Simplex Virus 1 Facilitates Productive Infection
Ma, Y., Jin, H., Vályi-Nagy, T., Cao, Y., Yan, Z., & He, B. (2011) · Journal of Virology · doi:10.1128/jvi.05376-11 · Cited by 80
Lohoefener, J., Steinke, N., Kay-Fedorov, P. C., Baruch, P., Никулин, А. Д., Tishchenko, S., Manstein, D. J., & Fedorov, R. (2015) · Structure · doi:10.1016/j.str.2015.03.012 · Cited by 81
Virulent Poxviruses Inhibit DNA Sensing by Preventing STING Activation
Georgana, I., Sumner, R. P., Towers, G. J., & de Motes, C. M. (2018) · Journal of Virology · doi:10.1128/jvi.02145-17 · Cited by 85
“(TBK)-1 and the downstream activation of IRFs and NF-κB (5-8).”
BackgroundBurroughs, A. M., & Aravind, L. (2020) · Journal of Bacteriology · doi:10.1128/jb.00365-20 · Cited by 78
MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway
Tian, M., Liu, W., Zhang, Q., Huang, Y., Li, W., Wang, W., Zhao, P., Huang, S., Song, Y., Shereen, M. A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108297 · Cited by 79
Wahaab, A., Mustafa, B. E., Hameed, M., Stevenson, N. J., Anwar, M. N., Liu, K., Wei, J., Qiu, Y., & Ma, Z. (2021) · Viruses · doi:10.3390/v14010044 · Cited by 81
Self-citationYing, X., Chen, Q., Yang, Y., Wu, Z., Zeng, W., Miao, C., Huang, Q., & Ai, K. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02186-6 · Cited by 87
Viral CNS infections: role of glial pattern recognition receptors in neuroinflammation
Furr, S. R., & Marriott, I. (2012) · Frontiers in Microbiology · doi:10.3389/fmicb.2012.00201 · Cited by 77
“Immunoprecipitation studies indicate STING associates with RIG-I complexes in close proximity to endoplasmic reticulum associated mitochondria (Ishikawa et al., 2009; Dixit et al., 2010).”
BackgroundProtein synthesis inhibition and GADD34 control IFN‐β heterogeneous expression in response to dsRNA
Dalet, A., Argüello, R. J., Combes, A. J., Spinelli, L., Jaeger, S., Fallet, M., Manh, T. V., Mendes, A. V., Perego, J., Reverendo, M., et al. (2017) · The EMBO Journal · doi:10.15252/embj.201695000 · Cited by 77
“…context than poly(I:C) and PKR activation by artificially activating stimulator of interferon genes (STING) with the cyclic dinucleotide cGAMP (Ishikawa et al , 2009). cGAMP, a dinucleotide normally produced by the DNA-binding protein cGAS (cGAMP synthase), has no documented effect on protein…”
Bode, C., Fox, M., Tewary, P., Steinhagen, A., Ellerkmann, R. K., Klinman, D., Baumgarten, G., Hornung, V., & Steinhagen, F. (2016) · European Journal of Immunology · doi:10.1002/eji.201546113 · Cited by 79
Sharma, S., & Fitzgerald, K. A. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1001310 · Cited by 79
“Most of these DNA sensors utilize a subset of adapter molecules, which relay signals to NF-κB and members of the interferon regulatory factor (IRF) family. TLR9 as well as DHX9 and DHX36 recruit MyD88 to activate IFN production in pDCs in response to DNA. In contrast, recognition of DNA by RNA-Pol III generates an RNA…”
BackgroundNi, J., Guo, T., Zhou, Y., Jiang, S., Zhang, L., & Zhu, Z. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04446-3 · Cited by 83
“Loss of cGAS or STING function significantly impairs the immune defense against these types of infections [8, 11, 12].”
BackgroundAntiviral role of grouper STING against iridovirus infection
Huang, Y., Ouyang, Z., Wang, W., Yu, Y., Li, P., Zhou, S. D., Wei, S., Wei, J., Huang, X., & Qin, Q. (2015) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2015.09.014 · Cited by 79
Conservation of the STING-Mediated Cytosolic DNA Sensing Pathway in Zebrafish
Ge, R., Zhou, Y., Peng, R., Wang, R., Li, M., Zhang, Y., Zheng, C., & Wang, C. (2015) · Journal of Virology · doi:10.1128/jvi.01049-15 · Cited by 79
“A STING knockout mouse is viable (25), and so is the STING-”
BackgroundInfluentialRIG-I Detects Triphosphorylated RNA of Listeria monocytogenes during Infection in Non-Immune Cells
Hagmann, C. A., Herzner, A., Abdullah, Z., Zillinger, T., Jakobs, C., Schuberth, C., Coch, C., Higgins, P. G., Wisplinghoff, H., Barchet, W., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062872 · Cited by 77
Loss of Trex1 in Dendritic Cells Is Sufficient To Trigger Systemic Autoimmunity
Peschke, K., Achleitner, M., Frenzel, K., Gerbaulet, A., Ada, S.-R., Zeller, N., Lienenklaus, S., Lesche, M., Poulet, C. E., Naumann, R., et al. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600722 · Cited by 82
“This adapter protein then signals activation of the IFN response (52).”
BackgroundHuman T-cell lymphotropic virus type 1 and its oncogenesis
Zhang, L.-L., Wei, J.-Y., Wang, L., Huang, S., & Chen, J. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.17 · Cited by 80
Cytosolic DNA‐sensing immune response and viral infection
Abe, T., Marutani, Y., & Shoji, I. (2019) · Microbiology and Immunology · doi:10.1111/1348-0421.12669 · Cited by 83
“consisting of multiple transmembrane regions; it is localized at the endoplasmic reticulum (ER) and plays an essential role in the cytosolic DNA-mediated innate immune response and the response of DNA-based immunization (23-25).”
Multifunctional STING‐Activating Mn3O4@Au‐dsDNA/DOX Nanoparticle for Antitumor Immunotherapy
Zhou, M., Wang, X., Lin, S., Cheng, Y., Zhao, S., Lin, J., Fang, Z., Lou, Z., Qin, L., & Wei, H. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202000064 · Cited by 80
Intramitochondrial Disulfide Polymerization Controls Cancer Cell Fate
Kim, S., Jana, B., Go, E. M., Lee, J. E., Jin, S., An, E., Hwang, J., Sim, Y., Son, S., Kim, D., et al. (2021) · ACS Nano · doi:10.1021/acsnano.1c04015 · Cited by 78
DNA Damage-Induced Inflammatory Microenvironment and Adult Stem Cell Response
Cinat, D., Coppes, R. P., & Barazzuol, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.729136 · Cited by 79
A TBK1-independent primordial function of STING in lysosomal biogenesis
Lv, B., Dion, W. A., Yang, H., Xun, J., Kim, D., Zhu, B., & Tan, J. X. (2024) · Molecular Cell · doi:10.1016/j.molcel.2024.08.026 · Cited by 84
Oshiumi, H., Ikeda, M., Matsumoto, M., Watanabe, A., Takeuchi, O., Akira, S., Kato, N., Shimotohno, K., & Seya, T. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014258 · Cited by 77
“In this context, we know LGP2 [41] and STING [42] act as positive regulators in virus infection.”
BackgroundParker, Z. M., Murphy, A. A., & Leib, D. A. (2015) · Journal of Virology · doi:10.1128/jvi.00954-15 · Cited by 76
“infection with 1 10(7) PFU HSV-1 strain KOS, while 75% of control mice survived (15).”
BackgroundResultInfluentialIntracellular STING inactivation sensitizes breast cancer cells to genotoxic agents
Gaston, J., Cheradame, L., Yvonnet, V., Déas, O., Poupon, M., Judde, J., Cairo, S., & Goffin, V. (2016) · Oncotarget · doi:10.18632/oncotarget.12858 · Cited by 75
“STING has been described to localize in the endoplasmic reticulum, the Golgi apparatus, perinuclear and autophagic vesicles [18, 24, 45].”
Hancks, D. C., Hartley, M. K., Hagan, C., Clark, N. L., & Elde, N. C. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005203 · Cited by 76
“cGAMP activates the STimulator of Interferon Genes (STING) [25, [29] [30] [31] , which in turn activates transcription of Type I Interferon genes through TBK1-IRF3 signals [8, 29] .”
BackgroundThe deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway
Zhang, L., Wei, N., Cui, Y., Hong, Z., Liu, X., Wang, Q., Li, S., Liu, H., Yu, H., Cai, Y., et al. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1007435 · Cited by 80
Interferons in Pain and Infections: Emerging Roles in Neuro-Immune and Neuro-Glial Interactions
Tan, P.-H., Ji, J., Yeh, C., & Ji, R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.783725 · Cited by 79
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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