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TLR7 Controls VSV Replication in CD169 + SCS Macrophages and Associated Viral Neuroinvasion.
- Source :
-
Frontiers in immunology [Front Immunol] 2019 Mar 15; Vol. 10, pp. 466. Date of Electronic Publication: 2019 Mar 15 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- Vesicular stomatitis virus (VSV) is an insect-transmitted rhabdovirus that is neurovirulent in mice. Upon peripheral VSV infection, CD169 <superscript>+</superscript> 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 <superscript>-/-</superscript> 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 <superscript>-/-</superscript> 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 <superscript>-/-</superscript> 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.
- Subjects :
- Animals
Brain immunology
Brain virology
Macrophages virology
Membrane Glycoproteins genetics
Mice
Mice, Knockout
Rhabdoviridae Infections genetics
Rhabdoviridae Infections pathology
Sialic Acid Binding Ig-like Lectin 1 genetics
Signal Transduction genetics
Signal Transduction immunology
Spinal Cord immunology
Spinal Cord virology
Toll-Like Receptor 7 genetics
Virus Replication genetics
Macrophages immunology
Membrane Glycoproteins immunology
Rhabdoviridae Infections immunology
Sialic Acid Binding Ig-like Lectin 1 immunology
Toll-Like Receptor 7 immunology
Vesiculovirus physiology
Virus Replication immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30930901
- Full Text :
- https://doi.org/10.3389/fimmu.2019.00466