The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
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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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
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AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
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IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
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Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
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VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling
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AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
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DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response
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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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