Cited by 123interferon and immune responsesImmune Response and InflammationDNA and Nucleic Acid Chemistry

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Cytosolic sensing of immuno-stimulatory DNA, the enemy within

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Dhanwani, Rekha, Takahashi, Mariko, Sharma, Sonia·2018·Current Opinion in Immunology

DOI 10.1016/j.coi.2017.11.004PMC PMC5916810

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Abstract

In the cytoplasm, DNA is sensed as a universal danger signal by the innate immune system. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor/enzyme that catalyzes formation of 2'-5'-cGAMP, an atypical cyclic di-nucleotide second messenger that binds and activates the Stimulator of Interferon Genes (STING), resulting in recruitment of Tank Binding Kinase 1 (TBK1), activation of the transcription factor Interferon Regulatory Factor 3 (IRF3), and trans-activation of innate immune response genes, including type I Interferon cytokines (IFN-I). Activation of the pro-inflammatory cGAS-STING-IRF3 response is triggered by direct recognition of the DNA genomes of bacteria and viruses, but also during RNA virus infection, neoplastic transformation, tumor immunotherapy and systemic auto-inflammatory diseases. In these circumstances, the source of immuno-stimulatory DNA has often represented a fundamental yet poorly understood aspect of the response. This review focuses on recent findings related to cGAS activation by an array of self-derived DNA substrates, including endogenous retroviral elements, mitochondrial DNA (mtDNA) and micronuclei generated as a result of genotoxic stress and DNA damage. These findings emphasize the role of the cGAS axis as a cell-intrinsic innate immune response to a wide variety of genomic insults.

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Authors: Dhanwani, R., Takahashi, M., & Sharma, S.
Affiliations: La Jolla Institute for Immunology (US)
Corresponding author: Sharma, Sonia
ORCID: Dhanwani, Rekha
Takahashi, Mariko
Sharma, Sonia
Venue: Current Opinion in Immunology
Publisher: Elsevier BV
Published: 2018-02
Volume: 50
Pages: 82-87
ISSN: 0952-7915 (ISSN-L)
DOI: 10.1016/j.coi.2017.11.004
PMC: PMC5916810
OpenAlex: W2771759088
Cited by: 123
References: 62
Citations by year: 2026: 6 · 2025: 9 · 2024: 17 · 2023: 15 · 2022: 16 · 2021: 15 · 2020: 17 · 2019: 17 · 2018: 11
FWCI: 1.26
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Current Opinion in Immunology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA199376)
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords: cGAS-STING pathway, cytosolic DNA sensing, STING, IRF3, type I interferon, innate immunity, endogenous retroviruses, mitochondrial DNA, micronuclei, genotoxic stress, DNA damage, cancer immunotherapy, autoinflammatory disease, RNA virus infection, oncogenic transformation
MeSH terms: Animals, Antigens, Cytosol, DNA, DNA Damage, Humans, Immunity, Immunity, Innate, Infections, Inflammation, Neoplasms, Host-Pathogen Interactions

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Cytosolic sensing of immuno-stimulatory DNA, the enemy within

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