牙周致病菌诱导的调节性B细胞的生成及分子机制研究

项目名称： 牙周致病菌诱导的调节性B细胞的生成及分子机制研究

项目编号： No.81470740

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 于晓潜

作者单位： 北京大学

项目金额： 73万元

中文摘要： 牙周炎是因菌斑与机体免疫间的平衡被打破而产生的疾病。牙龈卟啉单胞菌（P. gingivalis）可利用机体的免疫反应改变菌斑构成，进而导致骨吸收。具体机制尚不明确。前期研究表明，与多数细菌的脂多糖（LPS）不同，P. gingivalis LPS可同时活化B细胞的TLR-2和TLR4通路，其所诱导的IL-10(+) Breg不仅出现于传统的MZ和T2亚群，也出现在T1亚群。这可能有利于P.gingivalis逃避宿主免疫清除并为其它致病菌的增殖创造条件。本研究拟通过流式细胞技术确定P. gingivalis LPS诱导产生的Breg表型，以基因敲除小鼠和TLR PCR Array技术分析TLR2和TLR4途径在这一过程中的作用及相互影响。通过建立CD19-/-小鼠牙周炎模型及Breg过继转移模型，探讨P. gingivalis LPS诱导产生的Breg在牙周炎发生和发展中的作用。

中文关键词： 牙龈卟啉单胞菌脂多糖；调节性B细胞；Toll样受体；信号通路

英文摘要： Periodontitis is induced by the breakdown of the balance between biofilm and host immune system. Interacting with immune system, Porphyromonas gingivalis (P. gingivalis) leads to both an increase in the total bacterial load and changes in the composition of microbiota, followed by bone destruction. The detailed mechanism need to be clarified. In our previous study, P. gingivalis lipopolysaccharide (LPS) is different from other bacterial LPS in that it could activate both Toll-like receptor (TLR) 2 and TLR4 on B lymphocytes. The IL-10(+) regulatory B cells (Bregs) are distributed not only in proved subgroups like marginal zone (MZ) and T2 (transitional 2) but also in T1 B cells. This may contribute to the persistent infection of P. gingivalis and the uncontrolled growth of other bacterial species in the biofilm. In this study, we plan to define the surface marker of Breg under P. gingivalis LPS challenge using flow cytometry. The roles of TLR2, TLR4 and their crosstalk could be confirmed by knockout mice and PCR Array analysis. Furthermore, through CD19-/- periodontitis mouse model and adoptive transfer, the impact of P. gingivalis induced Bregs on the process of periodontitis will be investigated.

英文关键词： Porphyromonas gingivalis lipopolysaccharide;regulatory B cell;Toll-like receptor;signal pathway