Guggemoos Simone, Hangel Doris, Hamm Svetlana, Heit Antje, Bauer Stefan, Adler Heiko
Institute of Molecular Immunology, Clinical Cooperation Group Hematopoietic Cell Transplantation, GSF-National Research Center for Environment and Health, Munich, Germany.
J Immunol. 2008 Jan 1;180(1):438-43. doi: 10.4049/jimmunol.180.1.438.
The human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus and EBV cause important infections. As pathogenetic studies of the human infections are restricted, murine gammaherpesvirus 68 serves as a model to study gammaherpesvirus pathogenesis. TLRs are a conserved family of receptors detecting microbial molecular patterns. Among the TLRs, TLR9 recognizes unmethylated CpG DNA motifs present in bacterial and viral DNA. The aim of this study was to assess the role of TLR9 in gammaherpesvirus pathogenesis. Upon stimulation with murine gammaherpesvirus 68, Flt3L-cultured bone marrow cells (dendritic cells) from TLR9-/- mice secreted reduced levels of IL-12, IFN-alpha, and IL-6, when compared with dendritic cells from wild-type mice. Intranasal infection of TLR9-/- and wild-type mice did not reveal any differences during lytic and latent infection. In contrast, when infected i.p., TLR9-/- mice showed markedly higher viral loads both during lytic and latent infection. Thus, we show for the first time that TLR9 is involved in gammaherpesvirus pathogenesis and contributes to organ-specific immunity.
人类γ-疱疹病毒卡波西肉瘤相关疱疹病毒和EB病毒可引发重要感染。由于对人类感染的致病机制研究受到限制，小鼠γ-疱疹病毒68被用作研究γ-疱疹病毒致病机制的模型。Toll样受体（TLRs）是一类保守的受体家族，可检测微生物分子模式。在这些TLRs中，TLR9可识别细菌和病毒DNA中存在的未甲基化CpG DNA基序。本研究的目的是评估TLR9在γ-疱疹病毒致病机制中的作用。与野生型小鼠的树突状细胞相比，用小鼠γ-疱疹病毒68刺激后，来自TLR9基因敲除小鼠的Flt3L培养骨髓细胞（树突状细胞）分泌的IL-12、IFN-α和IL-6水平降低。对TLR9基因敲除小鼠和野生型小鼠进行鼻内感染，在裂解感染和潜伏感染期间未发现任何差异。相反，当通过腹腔注射感染时，TLR9基因敲除小鼠在裂解感染和潜伏感染期间均显示出明显更高的病毒载量。因此，我们首次表明TLR9参与γ-疱疹病毒致病机制并有助于器官特异性免疫。
