Human plasmacytoid dendritic cells elicit a Type I Interferon response by sensing DNA via the cGAS‐STING signaling pathway
Open accessAbstract
Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN) and are important for host defense by sensing microbial DNA via TLR9. pDCs also play a critical role in the pathogenesis of IFN‐driven autoimmune diseases. Yet, this autoimmune reaction is caused by the recognition of self‐DNA and has been linked to TLR9‐independent pathways. Increasing evidence suggests that the cytosolic DNA receptor cyclic GMP‐AMP (cGAMP) synthase (cGAS) is a critical component in the detection of pathogens and contributes to autoimmune diseases. It has been shown that binding of DNA to cGAS results in the synthesis of cGAMP and the subsequent activation of the stimulator of interferon genes (STING) adaptor to induce IFNs. Our results show that the cGAS‐STING pathway is expressed and activated in human pDCs by cytosolic DNA leading to a robust type I IFN response. Direct activation of STING by cyclic dinucleotides including cGAMP also activated pDCs and knockdown of STING abolished this IFN response. These results suggest that pDCs sense cytosolic DNA and cyclic dinucleotides via the cGAS‐STING pathway and that targeting this pathway could be of therapeutic interest.
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pDCs express high levels of TLR7 and TLR9 in their endosomes and the cytoplasmic DNA sensor cGAS, enabling detection of viral DNA and single-stranded RNA genomes and production of high amounts of IFN-I upon TLR or cGAS activation.
“pDCs express high levels of TLR7 and TLR9 in their endosomes as well as the cytoplasmic DNA sensor cGAS and are thus well equipped to detect viral DNA and single-stranded RNA genomes and produce high amounts of IFN-I upon TLR or cGAS activation.46,47,48,49”
From TLR9-independent CD8+ T cell responses in hepatic AAV gene transfer through IL-1R1-MyD88 signaling (2024) · cites this paper as [47]
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References 37 · Cited by 79
- Authors
- Bode, C., Fox, M., Tewary, P., Steinhagen, A., Ellerkmann, R. K., Klinman, D., Baumgarten, G., Hornung, V., & Steinhagen, F.
- Affiliations
- University of Bonn (DE)
- Leidos Biomedical Research Inc. (United States) (US)
- Frederick National Laboratory for Cancer Research (US)
- Corresponding author
- Bode, Christian
- ORCID
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2016-05-27
- Volume
- 46
- Issue
- 7
- Pages
- 1615-1621
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- PMC
- PMC6389263
- OpenAlex
- W2344846569
- Cited by
- 79
- References
- 37
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 12 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 14 · 2019: 11 · 2018: 5 · 2017: 6 · 2016: 2
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- University of Bonn (BONFOR)
- 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
- plasmacytoid dendritic cells, type I interferon, cGAS-STING pathway, cGAS, STING, cytosolic DNA sensing, cyclic dinucleotides, cGAMP
- MeSH terms
- STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Cells, Cultured, Cytosol, Dendritic Cells, DNA, Humans, Immunity, Innate, Interferon Type I, Membrane Proteins, Nucleotidyltransferases, Signal Transduction, Gene Expression, Interferon Regulatory Factor-3, Toll-Like Receptor 9
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