Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells

DOI PDF 被引用文献27件
  • Jennifer Lund
    1Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520
  • Ayuko Sato
    2Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520
  • Shizuo Akira
    3Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, SORST of Japan Science and Technology Corporation, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
  • Ruslan Medzhitov
    1Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520
  • Akiko Iwasaki
    1Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520

抄録

<jats:p>Plasmacytoid dendritic cells (pDCs) have been identified as a potent secretor of the type I interferons (IFNs) in response to CpG as well as several viruses. In this study, we examined the molecular mechanism of virus recognition by pDCs. First, we demonstrated that the CD11c+Gr-1intB220+ pDCs from mouse bone marrow secreted high levels of IFN-α in response to either live or UV-inactivated Herpes simplex virus-2 (HSV-2). Next, we identified that IFN-α secretion by pDCs required the expression of the adaptor molecule MyD88, suggesting the involvement of a Toll-like receptor (TLR) in HSV-2 recognition. To test whether a TLR mediates HSV-2–induced IFN-α secretion from pDCs, various knockout mice were examined. These experiments revealed a clear requirement for TLR9 in this process. Further, we demonstrated that purified HSV-2 DNA can trigger IFN-α secretion from pDCs and that inhibitory CpG oligonucleotide treatment diminished HSV-induced IFN-α secretion by pDCs in a dose-dependent manner. The recognition of HSV-2 by TLR9 was mediated through an endocytic pathway that was inhibited by chloroquine or bafilomycin A1. The strict requirement for TLR9 in IFN-α secretion was further confirmed by the inoculation of HSV-2 in vivo. Therefore, these results demonstrate a novel mechanism whereby the genomic DNA of a virus can engage TLR9 and result in the secretion of IFN-α by pDCs.</jats:p>

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