Your browser doesn't support javascript.
loading
TLR7 Controls VSV Replication in CD169+ SCS Macrophages and Associated Viral Neuroinvasion.
Solmaz, Gülhas; Puttur, Franz; Francozo, Marcela; Lindenberg, Marc; Guderian, Melanie; Swallow, Maxine; Duhan, Vikas; Khairnar, Vishal; Kalinke, Ulrich; Ludewig, Burkhard; Clausen, Björn E; Wagner, Hermann; Lang, Karl S; Sparwasser, Tim D.
Afiliação
  • Solmaz G; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
  • Puttur F; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
  • Francozo M; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
  • Lindenberg M; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
  • Guderian M; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
  • Swallow M; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
  • Duhan V; Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
  • Khairnar V; Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
  • Kalinke U; Institute of Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
  • Ludewig B; Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Clausen BE; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
  • Wagner H; Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich, Munich, Germany.
  • Lang KS; Institute of Immunology of the University Hospital in Essen, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
  • Sparwasser TD; Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
Front Immunol ; 10: 466, 2019.
Article em En | MEDLINE | ID: mdl-30930901
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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Replicação Viral / Glicoproteínas de Membrana / Vesiculovirus / Infecções por Rhabdoviridae / Receptor 7 Toll-Like / Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico / Macrófagos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Front Immunol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Temas: Geral Base de dados: MEDLINE Assunto principal: Replicação Viral / Glicoproteínas de Membrana / Vesiculovirus / Infecções por Rhabdoviridae / Receptor 7 Toll-Like / Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico / Macrófagos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Front Immunol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Alemanha