Retrovirology | |
Friend retrovirus drives cytotoxic effectors through Toll-like receptor 3 | |
Ulf Dittmer3  Mario L Santiago1  Mengji Lu3  Carsten J Kirchning2  Bradley S Barrett1  Michael S Harper1  Anna M Sigmund2  Sandra Francois3  Kathrin Gibbert3  | |
[1] Department of Medicine, University of Colorado Denver, Aurora 80045, CO, USA;Institute for Medical Microbiology of the University Hospital in Essen, University of Duisburg-Essen, Essen, Germany;Institute for Virology of the University Hospital in Essen, University of Duisburg-Essen, Essen, Germany | |
关键词: Pathogen recognition; Cytotoxic T cells; NK cells; Dendritic cells; Friend Retrovirus; Toll-like receptor 3; | |
Others : 1132008 DOI : 10.1186/s12977-014-0126-4 |
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received in 2014-10-24, accepted in 2014-12-05, 发布年份 2014 | |
【 摘 要 】
Background
Pathogen recognition drives host defense towards viral infections. Specific groups rather than single members of the protein family of pattern recognition receptors (PRRs) such as membrane spanning Toll-like receptors (TLRs) and cytosolic helicases might mediate sensing of replication intermediates of a specific virus species. TLR7 mediates host sensing of retroviruses and could significantly influence retrovirus-specific antibody responses. However, the origin of efficient cell-mediated immunity towards retroviruses is unknown. Double-stranded RNA intermediates produced during retroviral replication are good candidates for immune stimulatory viral products. Thus, we considered TLR3 as primer of cell-mediated immunity against retroviruses in vivo.
Results
Infection of mice deficient in TLR3 (TLR3−/−) with Friend retrovirus (FV) complex revealed higher viral loads during acute retroviral infection compared to wild type mice. TLR3−/− mice exhibited significantly lower expression levels of type I interferons (IFNs) and IFN-stimulated genes like Pkr or Ifi44, as well as reduced numbers of activated myeloid dendritic cells (DCs) (CD86+ and MHC-II+). DCs generated from FV-infected TLR3−/− mice were less capable of priming virus-specific CD8+ T cell proliferation. Moreover, cytotoxicity of natural killer (NK) cells as well as CD8+ T cells were reduced in vitro and in vivo, respectively, in FV-infected TLR3-/- mice.
Conclusions
TLR3 mediates antiretroviral cytotoxic NK cell and CD8+ T cell activity in vivo. Our findings qualify TLR3 as target of immune therapy against retroviral infections.
【 授权许可】
2014 Gibbert et al.; licensee BioMed Central.
【 预 览 】
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