Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.
Identifieur interne : 000633 ( Main/Exploration ); précédent : 000632; suivant : 000634Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.
Auteurs : Ryota Sato [Japon] ; Akihisa Kato [Japon] ; Takahiko Chimura [Japon] ; Shin-Ichiroh Saitoh [Japon] ; Takuma Shibata [Japon] ; Yusuke Murakami [Japon] ; Ryutaro Fukui [Japon] ; Kaiwen Liu [Japon] ; Yun Zhang [Japon] ; Jun Arii [Japon] ; Ge-Hong Sun-Wada [Japon] ; Yoh Wada [Japon] ; Tsuneo Ikenoue [Japon] ; Glen N. Barber [États-Unis] ; Toshiya Manabe [Japon] ; Yasushi Kawaguchi [Japon] ; Kensuke Miyake [Japon]Source :
- Nature immunology [ 1529-2916 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Cellules NIH 3T3 (MeSH), Complexe-2 cible mécanistique de la rapamycine (immunologie), Encéphalite à herpès simplex (immunologie), Herpèsvirus humain de type 1 (MeSH), Immunité innée (immunologie), Récepteur de type Toll-3 (immunologie), Souris (MeSH), Souris de lignée BALB C (MeSH), Souris de lignée C57BL (MeSH).
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , immunology : Mechanistic Target of Rapamycin Complex 2, Toll-Like Receptor 3.
- immunology : Encephalitis, Herpes Simplex, Immunity, Innate.
- Animals, Herpesvirus 1, Human, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, NIH 3T3 Cells.
Abstract
TLR3 is a sensor of double-stranded RNA that is indispensable for defense against infection with herpes simplex virus type 1 (HSV-1) in the brain. We found here that TLR3 was required for innate immune responses to HSV-1 in neurons and astrocytes. During infection with HSV-1, TLR3 recruited the metabolic checkpoint kinase complex mTORC2, which led to the induction of chemokines and trafficking of TLR3 to the cell periphery. Such trafficking enabled the activation of molecules (including mTORC1) required for the induction of type I interferons. Intracranial infection of mice with HSV-1 was exacerbated by impairment of TLR3 responses with an inhibitor of mTOR and was significantly 'rescued' by potentiation of TLR3 responses with an agonistic antibody to TLR3. These results suggest that the TLR3-mTORC2 axis might be a therapeutic target through which to combat herpes simplex encephalitis.
DOI: 10.1038/s41590-018-0203-2
PubMed: 30201994
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Murakami, Yusuke" sort="Murakami, Yusuke" uniqKey="Murakami Y" first="Yusuke" last="Murakami">Yusuke Murakami</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of 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Tokyo</orgName></affiliation></author><author><name sortKey="Liu, Kaiwen" sort="Liu, Kaiwen" uniqKey="Liu K" first="Kaiwen" last="Liu">Kaiwen Liu</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Zhang, Yun" sort="Zhang, Yun" uniqKey="Zhang Y" first="Yun" last="Zhang">Yun Zhang</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Arii, Jun" sort="Arii, Jun" uniqKey="Arii J" first="Jun" last="Arii">Jun Arii</name><affiliation wicri:level="4"><nlm:affiliation>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 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Sun-Wada</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyoto, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyoto</wicri:regionArea><wicri:noRegion>Kyoto</wicri:noRegion></affiliation></author><author><name sortKey="Wada, Yoh" sort="Wada, Yoh" uniqKey="Wada Y" first="Yoh" last="Wada">Yoh Wada</name><affiliation wicri:level="1"><nlm:affiliation>Division of Biological Science, Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Biological Science, Institute of Scientific and Industrial Research, Osaka University, Osaka</wicri:regionArea><wicri:noRegion>Osaka</wicri:noRegion></affiliation></author><author><name sortKey="Ikenoue, Tsuneo" sort="Ikenoue, Tsuneo" uniqKey="Ikenoue T" first="Tsuneo" last="Ikenoue">Tsuneo Ikenoue</name><affiliation wicri:level="4"><nlm:affiliation>Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Barber, Glen N" sort="Barber, Glen N" uniqKey="Barber G" first="Glen N" last="Barber">Glen N. Barber</name><affiliation wicri:level="2"><nlm:affiliation>UM/Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>UM/Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Manabe, Toshiya" sort="Manabe, Toshiya" uniqKey="Manabe T" first="Toshiya" last="Manabe">Toshiya Manabe</name><affiliation wicri:level="4"><nlm:affiliation>Division of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Kawaguchi, Yasushi" sort="Kawaguchi, Yasushi" uniqKey="Kawaguchi Y" first="Yasushi" last="Kawaguchi">Yasushi Kawaguchi</name><affiliation wicri:level="4"><nlm:affiliation>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ykawagu@ims.u-tokyo.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ykawagu@ims.u-tokyo.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Miyake, Kensuke" sort="Miyake, Kensuke" uniqKey="Miyake K" first="Kensuke" last="Miyake">Kensuke Miyake</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. kmiyake@ims.u-tokyo.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:30201994</idno><idno type="pmid">30201994</idno><idno type="doi">10.1038/s41590-018-0203-2</idno><idno type="wicri:Area/Main/Corpus">000456</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000456</idno><idno type="wicri:Area/Main/Curation">000456</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000456</idno><idno type="wicri:Area/Main/Exploration">000456</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.</title><author><name sortKey="Sato, Ryota" sort="Sato, Ryota" uniqKey="Sato R" first="Ryota" last="Sato">Ryota Sato</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Kato, Akihisa" sort="Kato, Akihisa" uniqKey="Kato A" first="Akihisa" last="Kato">Akihisa Kato</name><affiliation wicri:level="4"><nlm:affiliation>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Chimura, Takahiko" sort="Chimura, Takahiko" uniqKey="Chimura T" first="Takahiko" last="Chimura">Takahiko Chimura</name><affiliation wicri:level="4"><nlm:affiliation>Division of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Saitoh, Shin Ichiroh" sort="Saitoh, Shin Ichiroh" uniqKey="Saitoh S" first="Shin-Ichiroh" last="Saitoh">Shin-Ichiroh Saitoh</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Shibata, Takuma" sort="Shibata, Takuma" uniqKey="Shibata T" first="Takuma" last="Shibata">Takuma Shibata</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Murakami, Yusuke" sort="Murakami, Yusuke" uniqKey="Murakami Y" first="Yusuke" last="Murakami">Yusuke Murakami</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Fukui, Ryutaro" sort="Fukui, Ryutaro" uniqKey="Fukui R" first="Ryutaro" last="Fukui">Ryutaro Fukui</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Liu, Kaiwen" sort="Liu, Kaiwen" uniqKey="Liu K" first="Kaiwen" last="Liu">Kaiwen Liu</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Zhang, Yun" sort="Zhang, Yun" uniqKey="Zhang Y" first="Yun" last="Zhang">Yun Zhang</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Arii, Jun" sort="Arii, Jun" uniqKey="Arii J" first="Jun" last="Arii">Jun Arii</name><affiliation wicri:level="4"><nlm:affiliation>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Sun Wada, Ge Hong" sort="Sun Wada, Ge Hong" uniqKey="Sun Wada G" first="Ge-Hong" last="Sun-Wada">Ge-Hong Sun-Wada</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyoto, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyoto</wicri:regionArea><wicri:noRegion>Kyoto</wicri:noRegion></affiliation></author><author><name sortKey="Wada, Yoh" sort="Wada, Yoh" uniqKey="Wada Y" first="Yoh" last="Wada">Yoh Wada</name><affiliation wicri:level="1"><nlm:affiliation>Division of Biological Science, Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Biological Science, Institute of Scientific and Industrial Research, Osaka University, Osaka</wicri:regionArea><wicri:noRegion>Osaka</wicri:noRegion></affiliation></author><author><name sortKey="Ikenoue, Tsuneo" sort="Ikenoue, Tsuneo" uniqKey="Ikenoue T" first="Tsuneo" last="Ikenoue">Tsuneo Ikenoue</name><affiliation wicri:level="4"><nlm:affiliation>Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Barber, Glen N" sort="Barber, Glen N" uniqKey="Barber G" first="Glen N" last="Barber">Glen N. Barber</name><affiliation wicri:level="2"><nlm:affiliation>UM/Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>UM/Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL</wicri:regionArea><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Manabe, Toshiya" sort="Manabe, Toshiya" uniqKey="Manabe T" first="Toshiya" last="Manabe">Toshiya Manabe</name><affiliation wicri:level="4"><nlm:affiliation>Division of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Kawaguchi, Yasushi" sort="Kawaguchi, Yasushi" uniqKey="Kawaguchi Y" first="Yasushi" last="Kawaguchi">Yasushi Kawaguchi</name><affiliation wicri:level="4"><nlm:affiliation>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ykawagu@ims.u-tokyo.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ykawagu@ims.u-tokyo.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author><author><name sortKey="Miyake, Kensuke" sort="Miyake, Kensuke" uniqKey="Miyake K" first="Kensuke" last="Miyake">Kensuke Miyake</name><affiliation wicri:level="4"><nlm:affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. kmiyake@ims.u-tokyo.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName><orgName type="university">Université de Tokyo</orgName></affiliation></author></analytic><series><title level="j">Nature immunology</title><idno type="eISSN">1529-2916</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Encephalitis, Herpes Simplex (immunology)</term><term>Herpesvirus 1, Human (MeSH)</term><term>Immunity, Innate (immunology)</term><term>Mechanistic Target of Rapamycin Complex 2 (immunology)</term><term>Mice (MeSH)</term><term>Mice, Inbred BALB C (MeSH)</term><term>Mice, Inbred C57BL (MeSH)</term><term>NIH 3T3 Cells (MeSH)</term><term>Toll-Like Receptor 3 (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Cellules NIH 3T3 (MeSH)</term><term>Complexe-2 cible mécanistique de la rapamycine (immunologie)</term><term>Encéphalite à herpès simplex (immunologie)</term><term>Herpèsvirus humain de type 1 (MeSH)</term><term>Immunité innée (immunologie)</term><term>Récepteur de type Toll-3 (immunologie)</term><term>Souris (MeSH)</term><term>Souris de lignée BALB C (MeSH)</term><term>Souris de lignée C57BL (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Mechanistic Target of Rapamycin Complex 2</term><term>Toll-Like Receptor 3</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Complexe-2 cible mécanistique de la rapamycine</term><term>Encéphalite à herpès simplex</term><term>Immunité innée</term><term>Récepteur de type Toll-3</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Encephalitis, Herpes Simplex</term><term>Immunity, Innate</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Herpesvirus 1, Human</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred C57BL</term><term>NIH 3T3 Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules NIH 3T3</term><term>Herpèsvirus humain de type 1</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Souris de lignée C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">TLR3 is a sensor of double-stranded RNA that is indispensable for defense against infection with herpes simplex virus type 1 (HSV-1) in the brain. We found here that TLR3 was required for innate immune responses to HSV-1 in neurons and astrocytes. During infection with HSV-1, TLR3 recruited the metabolic checkpoint kinase complex mTORC2, which led to the induction of chemokines and trafficking of TLR3 to the cell periphery. Such trafficking enabled the activation of molecules (including mTORC1) required for the induction of type I interferons. Intracranial infection of mice with HSV-1 was exacerbated by impairment of TLR3 responses with an inhibitor of mTOR and was significantly 'rescued' by potentiation of TLR3 responses with an agonistic antibody to TLR3. These results suggest that the TLR3-mTORC2 axis might be a therapeutic target through which to combat herpes simplex encephalitis.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30201994</PMID><DateCompleted><Year>2019</Year><Month>04</Month><Day>22</Day></DateCompleted><DateRevised><Year>2019</Year><Month>08</Month><Day>24</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1529-2916</ISSN><JournalIssue CitedMedium="Internet"><Volume>19</Volume><Issue>10</Issue><PubDate><Year>2018</Year><Month>10</Month></PubDate></JournalIssue><Title>Nature immunology</Title><ISOAbbreviation>Nat Immunol</ISOAbbreviation></Journal><ArticleTitle>Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.</ArticleTitle><Pagination><MedlinePgn>1071-1082</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41590-018-0203-2</ELocationID><Abstract><AbstractText>TLR3 is a sensor of double-stranded RNA that is indispensable for defense against infection with herpes simplex virus type 1 (HSV-1) in the brain. We found here that TLR3 was required for innate immune responses to HSV-1 in neurons and astrocytes. During infection with HSV-1, TLR3 recruited the metabolic checkpoint kinase complex mTORC2, which led to the induction of chemokines and trafficking of TLR3 to the cell periphery. Such trafficking enabled the activation of molecules (including mTORC1) required for the induction of type I interferons. Intracranial infection of mice with HSV-1 was exacerbated by impairment of TLR3 responses with an inhibitor of mTOR and was significantly 'rescued' by potentiation of TLR3 responses with an agonistic antibody to TLR3. These results suggest that the TLR3-mTORC2 axis might be a therapeutic target through which to combat herpes simplex encephalitis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sato</LastName><ForeName>Ryota</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kato</LastName><ForeName>Akihisa</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chimura</LastName><ForeName>Takahiko</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saitoh</LastName><ForeName>Shin-Ichiroh</ForeName><Initials>SI</Initials><AffiliationInfo><Affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shibata</LastName><ForeName>Takuma</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Murakami</LastName><ForeName>Yusuke</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fukui</LastName><ForeName>Ryutaro</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Kaiwen</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Yun</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arii</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sun-Wada</LastName><ForeName>Ge-Hong</ForeName><Initials>GH</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyoto, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wada</LastName><ForeName>Yoh</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Biological Science, Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ikenoue</LastName><ForeName>Tsuneo</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Barber</LastName><ForeName>Glen N</ForeName><Initials>GN</Initials><AffiliationInfo><Affiliation>UM/Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Manabe</LastName><ForeName>Toshiya</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kawaguchi</LastName><ForeName>Yasushi</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ykawagu@ims.u-tokyo.ac.jp.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ykawagu@ims.u-tokyo.ac.jp.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Miyake</LastName><ForeName>Kensuke</ForeName><Initials>K</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-6629-226X</Identifier><AffiliationInfo><Affiliation>Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. kmiyake@ims.u-tokyo.ac.jp.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>09</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Nat Immunol</MedlineTA><NlmUniqueID>100941354</NlmUniqueID><ISSNLinking>1529-2908</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C519703">TLR3 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051196">Toll-Like Receptor 3</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000076225">Mechanistic Target of Rapamycin Complex 2</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020803" MajorTopicYN="N">Encephalitis, Herpes Simplex</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018259" MajorTopicYN="N">Herpesvirus 1, Human</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007113" MajorTopicYN="N">Immunity, Innate</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000076225" MajorTopicYN="N">Mechanistic Target of Rapamycin Complex 2</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051379" MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008807" MajorTopicYN="N">Mice, Inbred BALB C</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D041681" MajorTopicYN="N">NIH 3T3 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051196" MajorTopicYN="N">Toll-Like Receptor 3</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>09</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>07</Month><Day>31</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>9</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>4</Month><Day>23</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>9</Month><Day>12</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30201994</ArticleId><ArticleId IdType="doi">10.1038/s41590-018-0203-2</ArticleId><ArticleId IdType="pii">10.1038/s41590-018-0203-2</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Japon</li><li>États-Unis</li></country><region><li>Floride</li><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement><orgName><li>Université de Tokyo</li></orgName></list><tree><country name="Japon"><region name="Région de Kantō"><name sortKey="Sato, Ryota" sort="Sato, Ryota" uniqKey="Sato R" first="Ryota" last="Sato">Ryota Sato</name></region><name sortKey="Arii, Jun" sort="Arii, Jun" uniqKey="Arii J" first="Jun" last="Arii">Jun Arii</name><name sortKey="Arii, Jun" sort="Arii, Jun" uniqKey="Arii J" first="Jun" last="Arii">Jun Arii</name><name sortKey="Chimura, Takahiko" sort="Chimura, Takahiko" uniqKey="Chimura T" first="Takahiko" last="Chimura">Takahiko Chimura</name><name sortKey="Fukui, Ryutaro" sort="Fukui, Ryutaro" uniqKey="Fukui R" first="Ryutaro" last="Fukui">Ryutaro Fukui</name><name sortKey="Ikenoue, Tsuneo" sort="Ikenoue, Tsuneo" uniqKey="Ikenoue T" first="Tsuneo" last="Ikenoue">Tsuneo Ikenoue</name><name sortKey="Kato, Akihisa" sort="Kato, Akihisa" uniqKey="Kato A" first="Akihisa" last="Kato">Akihisa Kato</name><name sortKey="Kato, Akihisa" sort="Kato, Akihisa" uniqKey="Kato A" first="Akihisa" last="Kato">Akihisa Kato</name><name sortKey="Kawaguchi, Yasushi" sort="Kawaguchi, Yasushi" uniqKey="Kawaguchi Y" first="Yasushi" last="Kawaguchi">Yasushi Kawaguchi</name><name sortKey="Kawaguchi, Yasushi" sort="Kawaguchi, Yasushi" uniqKey="Kawaguchi Y" first="Yasushi" last="Kawaguchi">Yasushi Kawaguchi</name><name sortKey="Liu, Kaiwen" sort="Liu, Kaiwen" uniqKey="Liu K" first="Kaiwen" last="Liu">Kaiwen Liu</name><name sortKey="Manabe, Toshiya" sort="Manabe, Toshiya" uniqKey="Manabe T" first="Toshiya" last="Manabe">Toshiya Manabe</name><name sortKey="Miyake, Kensuke" sort="Miyake, Kensuke" uniqKey="Miyake K" first="Kensuke" last="Miyake">Kensuke Miyake</name><name sortKey="Murakami, Yusuke" sort="Murakami, Yusuke" uniqKey="Murakami Y" first="Yusuke" last="Murakami">Yusuke Murakami</name><name sortKey="Saitoh, Shin Ichiroh" sort="Saitoh, Shin Ichiroh" uniqKey="Saitoh S" first="Shin-Ichiroh" last="Saitoh">Shin-Ichiroh Saitoh</name><name sortKey="Shibata, Takuma" sort="Shibata, Takuma" uniqKey="Shibata T" first="Takuma" last="Shibata">Takuma Shibata</name><name sortKey="Sun Wada, Ge Hong" sort="Sun Wada, Ge Hong" uniqKey="Sun Wada G" first="Ge-Hong" last="Sun-Wada">Ge-Hong Sun-Wada</name><name sortKey="Wada, Yoh" sort="Wada, Yoh" uniqKey="Wada Y" first="Yoh" last="Wada">Yoh Wada</name><name sortKey="Zhang, Yun" sort="Zhang, Yun" uniqKey="Zhang Y" first="Yun" last="Zhang">Yun Zhang</name></country><country name="États-Unis"><region name="Floride"><name sortKey="Barber, Glen N" sort="Barber, Glen N" uniqKey="Barber G" first="Glen N" last="Barber">Glen N. Barber</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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