Division of Infectious Diseases and Immunology, Department of Medicine
Immunology and Infectious Disease | Nervous System Diseases | Virus Diseases
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.
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Copyright © 2016, The Author(s). Citation: Nat Commun. 2016 Nov 10;7:13348. doi: 10.1038/ncomms13348. Link to article on publisher's site
DOI of Published Version
Glial biology, Infectious diseases, Interferons, Viral host response
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.; and Paludan, Soren R., "Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS" (2016). Open Access Articles. 2995.
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