期刊
FRONTIERS IN IMMUNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.00466
关键词
pattern recognition receptors; Toll-like receptor 7; vesicular stomatitis virus; virus replication; innate immunity; subcapsular sinus macrophages; subcutaneous infection; conditional knock-out mice
类别
资金
- Hannover Biomedical Research School (HBRS)
- Center for Infection Biology (ZIB)
- Hannover Medical School (MHH)
- fellowship Ciencias sem Fronteiras/DAAD
- German Center for Infection Research
- Braukmann-Wittenberg-Herz-Stiftung and Deutsche Forschungsgemeinschaft
- Deutsche Forschungsgemeinschaft [SFB-900 (Sonderforschungsbereich 900)]
- HiLF grant
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.
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