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TLR7 Controls VSV Replication in CD169 SCS Macrophages and Associated Viral Neuroinvasion

Gülhas Solmaz, Franz Puttur, Marcela Francozo, Marc Lindenberg, Melanie Guderian, Maxine Swallow, Vikas Duhan, Vishal Khairnar, Ulrich Kalinke, Burkhard Ludewig, Björn E Clausen, Hermann Wagner, Karl S Lang & Tim D Sparwasser

abstract Vesicular 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.
   
citation Solmaz G, Puttur F, Francozo M, Lindenberg M, Guderian M, Swallow M, Duhan V, Khairnar V, Kalinke U, Ludewig B, Clausen B E, Wagner H, Lang K S, Sparwasser T D. TLR7 Controls VSV Replication in CD169 SCS Macrophages and Associated Viral Neuroinvasion. Front Immunol 2019; 10:466.
   
type journal paper/review (English)
date of publishing 15-03-2019
journal title Front Immunol (10)
ISSN electronic 1664-3224
pages 466
PubMed 30930901
DOI 10.3389/fimmu.2019.00466