Jens Randel Nyengaard

Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS

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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.

In: Nature Communications, Vol. 7, 13348, 10.11.2016.

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@article{ff6c26e947a942939b6a7625731de228,
title = "Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS",
abstract = "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.",
author = "Reinert, {Line S} and Katar{\'i}na Lopu{\v s}n{\'a} and Henriette Winther and Chenglong Sun and Thomsen, {Martin K} and Ramya Nandakumar and Mogensen, {Trine H} and Morten Meyer and Christian V{\ae}gter and Nyengaard, {Jens R} and Fitzgerald, {Katherine A} and Paludan, {S{\o}ren R}",
year = "2016",
month = nov,
day = "10",
doi = "10.1038/ncomms13348",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Sensing of HSV-1 by the cGAS-STING pathway in microglia orchestrates antiviral defence in the CNS

AU - Reinert, Line S

AU - Lopušná, Katarína

AU - Winther, Henriette

AU - Sun, Chenglong

AU - Thomsen, Martin K

AU - Nandakumar, Ramya

AU - Mogensen, Trine H

AU - Meyer, Morten

AU - Vægter, Christian

AU - Nyengaard, Jens R

AU - Fitzgerald, Katherine A

AU - Paludan, Søren R

PY - 2016/11/10

Y1 - 2016/11/10

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms13348

DO - 10.1038/ncomms13348

M3 - Journal article

C2 - 27830700

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 13348

ER -