TLR9-independent activation of B lymphocytes by bacterial DNA
TLR9-independent activation of B lymphocytes by bacterial DNA
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DOI：
10.1089/dna.2006.25.253
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发表时间：
2006-05-01
影响因子：
3.1
通讯作者：
Zanetti, Maurizio
中科院分区：
文献类型：
--
作者：
Cortez-Gonzalez, Xochitl;Pellicciotta, Ilenia;Zanetti, Maurizio
细胞内Toll样受体9（TLR 9）在其识别在CpG基序处未甲基化的单链DNA的能力方面是独特的。该实验室的工作表明质粒DNA在B淋巴细胞中自发内化。该事件之后是共刺激分子的上调和这些细胞获得抗原呈递功能。然而，目前尚不清楚这种现象是否依赖于TLR 9。由于基于DNA的药物在免疫治疗和疫苗接种中发挥的相关作用，以及CpG基序对TLR 9信号传导的核心作用，我们决定研究通过TLR 9的信号传导是否是淋巴细胞自发转基因的先决条件。在这里，我们发现，转基因表达和上调的CD 40和CD 86共刺激分子并没有抑制氯喹治疗。在来自TLR 9（-/-）小鼠的B淋巴细胞中也发生自发转基因，并且在C57 BI/6小鼠中注射TLR 9（-/-）转基因B淋巴细胞诱导的CD 4和CD 8 T细胞应答与野生型B淋巴细胞诱导的那些相当。总的来说，这些结果表明质粒DNA通过TLR 9非依赖性途径激活哺乳动物B淋巴细胞。
The intracellular Toll-like receptor 9 (TLR9) is unique in its ability to recognize single-stranded DNA unmethylated at CpG motifs. Work from this laboratory showed that plasmid DNA is spontaneously internalized in B lymphocytes. This event is followed by the upregulation of costimulatory molecules and the acquisition of antigen presenting function by these cells. However, it is not known whether this phenomenon depends on TLR9. Because of the relevant role played by DNA-based drugs in immunotherapy and vaccination, and the central role of TLR9 signaling by CpG motifs, we decided to investigate whether signaling through TLR9 is a prerequisite for spontaneous transgenesis of lymphocytes. Here we found that transgene expression and upregulation of CD40 and CD86 costimulatory molecules was not inhibited by chloroquine treatment. Spontaneous transgenesis also occurred in B lymphocytes from TLR9(-/-) mice, and the injection of TLR9(-/-) transgenic B lymphocytes in C57BI/6 mice induced both CD4 and CD8 T cell responses comparable to those induced by wild-type B lymphocytes. Collectively, these results suggest that plasmid DNA activates mammalian B lymphocytes through a TLR9 independent pathway.