Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS
Authors
Reinert, Line S.Lopusna, Katarina
Winther, Henriette
Sun, Chenglong
Thomsen, Martin K.
Nandakumar, Ramya
Mogensen, Trine H.
Meyer, Morten
Vaegter, Christian
Nyengaard, Jens R.
Fitzgerald, Katherine A.
Paludan, Soren R.
UMass Chan Affiliations
Division of Infectious Diseases and Immunology, Department of MedicineDocument Type
Journal ArticlePublication Date
2016-11-10Keywords
Glial biologyInfectious diseases
Interferons
Viral host response
Immunology and Infectious Disease
Nervous System Diseases
Virus Diseases
Metadata
Show full item recordAbstract
Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication is strongly increased in neurons in STING-deficient mice. Interestingly, HSV-infected microglia confer STING-dependent antiviral activities in neurons and prime type I IFN production in astrocytes through the TLR3 pathway. Thus, sensing of HSV-1 infection in the CNS by microglia through the cGAS-STING pathway orchestrates an antiviral program that includes type I IFNs and immune-priming of other cell types.Source
Nat Commun. 2016 Nov 10;7:13348. doi: 10.1038/ncomms13348. Link to article on publisher's siteDOI
10.1038/ncomms13348Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40197PubMed ID
27830700Related Resources
Link to Article in PubMedRights
Copyright © 2016, The Author(s).Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1038/ncomms13348