Friend retrovirus drives cytotoxic effectors through Toll-like receptor 3
Retrovirology(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.
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关键词
Toll-like receptor 3,Friend Retrovirus,Dendritic cells,NK cells,Cytotoxic T cells,Pathogen recognition
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