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STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
- Source :
- Nature. 461:788-792
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- 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)1–3. 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 infection4. 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.
- Subjects :
- DNA, Bacterial
Intracellular Space
Vesicular Transport Proteins
Antigen-Presenting Cells
Herpesvirus 1, Human
Protein Serine-Threonine Kinases
Biology
Endoplasmic Reticulum
Article
Microbiology
Mice
Interferon
Vaccines, DNA
medicine
Animals
Mice, Knockout
Multidisciplinary
Innate immune system
Cyclic GMP-AMP synthase
Cytoplasmic Vesicles
Cytosolic DNA-Sensing Pathway
Membrane Proteins
DNA virus
Fibroblasts
Listeria monocytogenes
Virology
Immunity, Innate
eye diseases
Protein Transport
Sting
Stimulator of interferon genes
DNA, Viral
Interferon Type I
Interferon type I
Plasmids
T-Lymphocytes, Cytotoxic
medicine.drug
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 461
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....6d4d932941bc91fc22538c20bd66b936