| Literature DB >> 30201994 |
Ryota Sato1, Akihisa Kato2,3, Takahiko Chimura4, Shin-Ichiroh Saitoh1, Takuma Shibata1, Yusuke Murakami1, Ryutaro Fukui1, Kaiwen Liu1, Yun Zhang1, Jun Arii2,3, Ge-Hong Sun-Wada5, Yoh Wada6, Tsuneo Ikenoue7, Glen N Barber8, Toshiya Manabe4, Yasushi Kawaguchi9,10, Kensuke Miyake11.
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.Entities:
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Year: 2018 PMID： 30201994 DOI： 10.1038/s41590-018-0203-2
Source DB: PubMed Journal: Nat Immunol ISSN： 1529-2908 Impact factor: 25.606