Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS
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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Online |
| Language: | English |
| Published: |
Nature Publishing Group
2016
|
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109551/ |
| id |
pubmed-5109551 |
|---|---|
| recordtype |
oai_dc |
| spelling |
pubmed-51095512017-01-13 Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS Reinert, Line S. Lopušná, Katarína Winther, Henriette Sun, Chenglong Thomsen, Martin K. Nandakumar, Ramya Mogensen, Trine H. Meyer, Morten Vægter, Christian Nyengaard, Jens R. Fitzgerald, Katherine A. Paludan, Søren R. Article 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. Nature Publishing Group 2016-11-10 /pmc/articles/PMC5109551/ /pubmed/27830700 http://dx.doi.org/10.1038/ncomms13348 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Reinert, Line S. Lopušná, Katarína Winther, Henriette Sun, Chenglong Thomsen, Martin K. Nandakumar, Ramya Mogensen, Trine H. Meyer, Morten Vægter, Christian Nyengaard, Jens R. Fitzgerald, Katherine A. Paludan, Søren R. |
| spellingShingle |
Reinert, Line S. Lopušná, Katarína Winther, Henriette Sun, Chenglong Thomsen, Martin K. Nandakumar, Ramya Mogensen, Trine H. Meyer, Morten Vægter, Christian Nyengaard, Jens R. Fitzgerald, Katherine A. Paludan, Søren R. Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS |
| author_facet |
Reinert, Line S. Lopušná, Katarína Winther, Henriette Sun, Chenglong Thomsen, Martin K. Nandakumar, Ramya Mogensen, Trine H. Meyer, Morten Vægter, Christian Nyengaard, Jens R. Fitzgerald, Katherine A. Paludan, Søren R. |
| author_sort |
Reinert, Line S. |
| title |
Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS |
| title_short |
Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS |
| title_full |
Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS |
| title_fullStr |
Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS |
| title_full_unstemmed |
Sensing of HSV-1 by the cGAS–STING pathway in microglia orchestrates antiviral defence in the CNS |
| title_sort |
sensing of hsv-1 by the cgas–sting pathway in microglia orchestrates antiviral defence in the cns |
| description |
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. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109551/ |
| _version_ |
1613727357566189568 |