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dc.contributor.authorSolmaz, Gülhas
dc.contributor.authorPuttur, Franz
dc.contributor.authorFrancozo, Marcela
dc.contributor.authorLindenberg, Marc
dc.contributor.authorGuderian, Melanie
dc.contributor.authorSwallow, Maxine
dc.contributor.authorDuhan, Vikas
dc.contributor.authorKhairnar, Vishal
dc.contributor.authorKalinke, Ulrich
dc.contributor.authorLudewig, Burkhard
dc.contributor.authorClausen, Björn E
dc.contributor.authorWagner, Hermann
dc.contributor.authorLang, Karl S
dc.contributor.authorSparwasser, Tim D
dc.date.accessioned2019-06-07T08:39:07Z
dc.date.available2019-06-07T08:39:07Z
dc.date.issued2019-01-01
dc.identifier.citationFront Immunol. 2019 Mar 15;10:466. doi: 10.3389/fimmu.2019.00466. eCollection 2019.en_US
dc.identifier.issn1664-3224
dc.identifier.pmid30930901
dc.identifier.urihttp://hdl.handle.net/10033/621805
dc.description.abstractVesicular stomatitis virus (VSV) is an insect-transmitted rhabdovirus that is neurovirulent in mice. Upon peripheral VSV infection, CD169+ subcapsular sinus (SCS) macrophages capture VSV in the lymph, support viral replication, and prevent CNS neuroinvasion. To date, the precise mechanisms controlling VSV infection in SCS macrophages remain incompletely understood. Here, we show that Toll-like receptor-7 (TLR7), the main sensing receptor for VSV, is central in controlling lymph-borne VSV infection. Following VSV skin infection, TLR7-/- mice display significantly less VSV titers in the draining lymph nodes (dLN) and viral replication is attenuated in SCS macrophages. In contrast to effects of TLR7 in impeding VSV replication in the dLN, TLR7-/- mice present elevated viral load in the brain and spinal cord highlighting their susceptibility to VSV neuroinvasion. By generating novel TLR7 floxed mice, we interrogate the impact of cell-specific TLR7 function in anti-viral immunity after VSV skin infection. Our data suggests that TLR7 signaling in SCS macrophages supports VSV replication in these cells, increasing LN infection and may account for the delayed onset of VSV-induced neurovirulence observed in TLR7-/- mice. Overall, we identify TLR7 as a novel and essential host factor that critically controls anti-viral immunity to VSV. Furthermore, the novel mouse model generated in our study will be of valuable importance to shed light on cell-intrinsic TLR7 biology in future studies.en_US
dc.language.isoenen_US
dc.publisherFrontiersen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectToll-like receptor 7en_US
dc.subjectconditional knock-out miceen_US
dc.subjectinnate immunityen_US
dc.subjectpattern recognition receptorsen_US
dc.subjectsubcapsular sinus macrophagesen_US
dc.subjectsubcutaneous infectionen_US
dc.subjectvesicular stomatitis virusen_US
dc.subjectvirus replicationen_US
dc.titleTLR7 Controls VSV Replication in CD169 SCS Macrophages and Associated Viral Neuroinvasion.en_US
dc.typeArticleen_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalFrontiers in immunologyen_US
refterms.dateFOA2019-06-07T08:39:07Z
dc.source.journaltitleFrontiers in immunology


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