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  4. Activation of the STING-dependent type I interferon response reduces microglial reactivity and neuroinflammation
 
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research article

Activation of the STING-dependent type I interferon response reduces microglial reactivity and neuroinflammation

Mathus, Vidhu
•
Burai, Ritwik  
•
Vest, Ryan
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2017
Neuron

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 IFN beta, 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.

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Type
research article
DOI
10.1016/j.neuron.2017.11.032
Web of Science ID

WOS:000418900200013

Author(s)
Mathus, Vidhu
•
Burai, Ritwik  
•
Vest, Ryan
•
Bonanno, Liana
•
Lehallier, Benoit
•
Zardeneta, Macy
•
Mistry, Karishma
•
Do, Danny
•
Marsh, Samuel
•
Abud, Edsel M
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Date Issued

2017

Publisher

Cell Press

Published in
Neuron
Volume

96

Issue

6

Start page

1290

End page

1302.e6

Subjects

STING

•

Microglial

•

Neuroinflammation

•

Ganciclovir

•

Neuroprotection

URL

URL

http://www.cell.com/neuron/comments/S0896-6273(17)31085-1
Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LMNN  
Available on Infoscience
November 28, 2017
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/142366
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