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

@article{citeulike:3057987, abstract = {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-{alpha} in response to either live or UV-inactivated Herpes simplex virus-2 (HSV-2). Next, we identified that IFN-{alpha} 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-{alpha} 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-{alpha} secretion from pDCs and that inhibitory CpG oligonucleotide treatment diminished HSV-induced IFN-{alpha} 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-{alpha} 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-{alpha} by pDCs. 10.1084/jem.20030162}, author = {Lund, Jennifer and Sato, Ayuko and Akira, Shizuo and Medzhitov, Ruslan and Iwasaki, Akiko}, citeulike-article-id = {3057987}, citeulike-linkout-0 = {http://dx.doi.org/10.1084/jem.20030162}, citeulike-linkout-1 = {http://www.jem.org/cgi/content/abstract/198/3/513}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/12900525}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=12900525}, day = {4}, doi = {10.1084/jem.20030162}, journal = {J. Exp. Med.}, keywords = {dc, dna, herpesvirus, hsv-2, inhibitory, plasmacytoid, tlr9}, month = {August}, number = {3}, pages = {513--520}, posted-at = {2008-07-30 00:36:37}, priority = {0}, title = {Toll-like Receptor 9-mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells}, url = {http://dx.doi.org/10.1084/jem.20030162}, volume = {198}, year = {2003} }

TY - JOUR ID - citeulike:3057987 L3 - citeulike-article-id:3057987 N2 - 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-{alpha} in response to either live or UV-inactivated Herpes simplex virus-2 (HSV-2). Next, we identified that IFN-{alpha} 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-{alpha} 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-{alpha} secretion from pDCs and that inhibitory CpG oligonucleotide treatment diminished HSV-induced IFN-{alpha} 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-{alpha} 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-{alpha} by pDCs. 10.1084/jem.20030162 IS - 3 JF - J. Exp. Med. EP - 520 TI - Toll-like Receptor 9-mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells VL - 198 SP - 513 KW - dc KW - dna KW - herpesvirus KW - hsv-2 KW - inhibitory KW - plasmacytoid KW - tlr9 AU - Lund, Jennifer AU - Sato, Ayuko AU - Akira, Shizuo AU - Medzhitov, Ruslan AU - Iwasaki, Akiko PY - 2003/08/04/ UR - http://dx.doi.org/10.1084/jem.20030162 ER -