Related Experiment Video
Updated: Feb 16, 2026
Magnetic Isolation of Microglial Cells from Neonate Mouse for Primary Cell Cultures
Published on: July 25, 2022
Activation of the STING-Dependent Type I Interferon Response Reduces Microglial Reactivity and Neuroinflammation
Vidhu Mathur1, Ritwik Burai2, Ryan T Vest3
1Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA 94305, USA; Center for Tissue Regeneration, Repair and Rehabilitation, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
Abstract:
Brain aging and neurodegeneration are associated with prominent microglial reactivity and activation of innate immune response pathways, commonly referred to as neuroinflammation. One such pathway, the type I interferon response, recognizes viral or mitochondrial DNA in the cytoplasm via activation of the recently discovered cyclic dinucleotide synthetase cGAS and the cyclic dinucleotide receptor STING. Here we show that the FDA-approved antiviral drug ganciclovir (GCV) induces a type I interferon response independent of its canonical thymidine kinase target. Inhibition of components of the STING pathway, including STING, IRF3, Tbk1, extracellular IFNβ, and the Jak-Stat pathway resulted in reduced activity of GCV and its derivatives. Importantly, functional STING was necessary for GCV to inhibit inflammation in cultured myeloid cells and in a mouse model of multiple sclerosis. Collectively, our findings uncover an unexpected new activity of GCV and identify the STING pathway as a regulator of microglial reactivity and neuroinflammation.
Insights
The antiviral drug ganciclovir (GCV) activates the STING pathway, a key part of the innate immune response. This unexpected action of GCV helps reduce neuroinflammation, offering new therapeutic possibilities for brain aging and neurodegeneration.
Area of Science:
- Neuroimmunology
- Innate Immune Response
- Neuroinflammation
Background:
- Brain aging and neurodegeneration involve microglial activation and neuroinflammation.
- The type I interferon response, mediated by cGAS-STING, is a key innate immune pathway.
- This pathway recognizes cytoplasmic DNA, triggering immune responses.
Purpose of the Study:
- To investigate the mechanism of action of ganciclovir (GCV) beyond its antiviral activity.
- To explore the role of the STING pathway in GCV's effects on neuroinflammation.
- To identify potential therapeutic applications of GCV in neuroinflammatory conditions.
Main Methods:
- Assessed GCV's induction of type I interferon response.
- Inhibited components of the STING pathway (STING, IRF3, Tbk1, IFNβ, Jak-Stat).
- Evaluated GCV's anti-inflammatory effects in myeloid cells and a mouse model of multiple sclerosis.
Main Results:
- GCV induced a type I interferon response independently of its known thymidine kinase target.
- Inhibition of STING pathway components reduced GCV's activity and anti-inflammatory effects.
- Functional STING was essential for GCV to suppress inflammation in cellular and animal models.
Conclusions:
- GCV possesses an unexpected function in activating the STING pathway.
- The STING pathway regulates microglial reactivity and neuroinflammation.
- GCV's STING-dependent activity presents a novel therapeutic strategy for neuroinflammatory diseases.
Related Concept Videos
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...