Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases
Abstract
Plasmacytoid dendritic cells (pDCs) are important mediators of antiviral immunity through their ability to produce large amounts of type I interferons (IFNs) on viral infection. This function of pDCs is linked to their expression of Toll-like receptor 7 (TLR7) and TLR9, which sense viral nucleic acids within the early endosomes. Exclusion of self nucleic acids from TLR-containing early endosomes normally prevents pDC responses to them. However, in some autoimmune diseases, self nucleic acids can be modified by host factors and gain entrance to pDC endosomes, where they activate TLR signalling. Several pDC receptors negatively regulate type I IFN responses by pDCs during viral infection and for normal homeostasis.
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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 [49]
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- Authors
- Gilliet, M., Cao, W., & Liu, Y.-J.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Liu, Yong-Jun
- Venue
- Nature Reviews Immunology
- Published
- 2008-08
- Volume
- 8
- Issue
- 8
- Pages
- 594-606
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2046204077
- Cited by
- 1,190
- References
- 169
- Citations by year
- 2026: 28 · 2025: 26 · 2024: 38 · 2023: 42 · 2022: 46 · 2021: 57 · 2020: 57 · 2019: 64 · 2018: 76 · 2017: 65 · 2016: 75 · 2015: 59 · 2014: 86 · 2013: 94 · 2012: 108
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI074809)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- plasmacytoid dendritic cells, type I interferon, antiviral immunity, TLR7, TLR9, viral nucleic acids, autoimmune disease, early endosomes, nucleic acid sensing
- MeSH terms
- Autoimmune Diseases, Dendritic Cells, Humans, Immunity, Innate, Interferon Type I, Nucleic Acids, Virus Diseases, Signal Transduction, Adaptor Proteins, Vesicular Transport, Toll-Like Receptors, Myeloid Differentiation Factor 88
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