TLR9 contributes to antiviral immunity during gammaherpesvirus infection
TLR9 contributes to antiviral immunity during gammaherpesvirus infection
复制标题
DOI：
10.4049/jimmunol.180.1.438
复制
发表时间：
2008-01-01
影响因子：
4.4
通讯作者：
Adler, Heiko
中科院分区：
文献类型：
--
作者：
Guggemoos, Simone;Hangel, Doris;Adler, Heiko
人类伽玛疱疹病毒卡波西肉瘤相关疱疹病毒和EBV引起重要感染。由于人类感染的发病机制研究有限，鼠γ疱疹病毒68可以作为研究γ疱疹病毒发病机制的模型。tlr是一种保守的检测微生物分子模式的受体家族。在这些tlr中，TLR9识别存在于细菌和病毒DNA中的未甲基化CpG DNA基序。本研究的目的是评估TLR9在γ疱疹病毒发病机制中的作用。在小鼠γ疱疹病毒68刺激下，与野生型小鼠的树突状细胞相比，fit3l培养的TLR9（-/-）小鼠骨髓细胞（树突状细胞）分泌的IL-12、ifn - α和IL-6水平降低。TLR9（-/-）和野生型小鼠的鼻内感染在溶解性和潜伏性感染期间没有任何差异。相比之下，当感染i.p时，TLR9（-/-）小鼠在裂解和潜伏感染期间均表现出明显更高的病毒载量。因此，我们首次发现TLR9参与了γ疱疹病毒的发病机制，并有助于器官特异性免疫。
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, FIt3L-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.