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Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Hiroki Ishikawa1, Zhe Ma, Glen N Barber
1Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Nature
|September 25, 2009
Summary
The stimulator of interferon genes (STING) protein is essential for the innate immune system to detect intracellular DNA from pathogens like herpes simplex virus 1. STING activation is crucial for mounting effective host defense and vaccine responses.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- The innate immune system provides early defense against pathogens.
- Type I interferon (IFN) production is a key host defense mechanism.
- Mechanisms of innate immune response to intracellular DNA are not fully understood.
Purpose of the Study:
- To investigate the role of STING in the innate immune response to intracellular DNA.
- To elucidate the function of STING in host defense against DNA pathogens.
- To assess the impact of STING on DNA-based vaccine efficacy.
Main Methods:
- Utilized murine embryonic fibroblasts, macrophages, and dendritic cells.
- Infection models with herpes simplex virus 1 (HSV-1), Listeria monocytogenes, and B-form DNA.
- Employed STING-knockout mice for in vivo studies.
- Analyzed cytotoxic T-cell responses in DNA-vaccinated animals.
- Investigated STING and TBK1 localization within cells.
Main Results:
- STING is critical for IFN production in response to intracellular DNA from pathogens.
- Sting-knockout mice exhibit susceptibility to lethal HSV-1 infection.
- STING deficiency impairs cytotoxic T-cell responses to DNA vaccination.
- STING relocates with TBK1 to perinuclear vesicles upon encountering intracellular DNA.
Conclusions:
- STING is essential for innate immune defense against DNA pathogens like HSV-1.
- STING plays a vital role in facilitating the adjuvant effects of DNA vaccines.
- STING acts as a key sensor and transducer of intracellular DNA signals for immune activation.
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