牙龈卟啉单胞菌脂多糖体内诱导IL-10生成细胞在引起牙周炎方面的作用研究

Periodontitis, one of common oral diseases, is a chronic infection caused by bacteria in dental plaque, and is also the main reason for tooth loss of adults in our nation. As the main pathogen for inducing periodontitis, Porphyromonas gingivalis (P. gingivalis) plays an important role in periodontal tissue destruction, and has become one of the focuses in domestic and foreign scholars’ researches in recent years. Interlukin-10 (IL-10) is a potent anti-inflammatory cytokine that suppresses both immunoproliferative and inflammatory responses. Our previous data shows that Porphyromonas gingivalis lipopolysaccharides (P.g LPS) treatment couldn’t induce activation of spleen dendritic cell (DC) and NK cell in the mouse in vivo compared to Escherichia coli lipopolysaccharides (E.c LPS), but it can significantly increase the production of IL-10 both in the serum and splenocytes mRNA levels. However, which subset of cell in spleen can produce IL-10 and what is the role of this IL-10 in the early time point leading to P. gingivalis escape the host immune response has not well studied. In this study, we will examine the cell type which produce IL-10 response to P.g LPS treatment by flow cytometry and specific cell isolation kit and define the receptors which related with IL-10 production by gene knockout mice (TLR-2-/-,TLR-4-/- and MyD88-/-) which we already have. Finally by specific cell depletion or knockout mice, we will detect the role of P.g LPS-mediated IL-10-producing cells in periodontitis mouse model. These investigations may help to understand the mechanism of how P. gingivalis escape the host immune response.

牙周炎是目前公认全球发病率最高的口腔疾病，主要病原菌为牙龈卟啉单胞菌，可导致成年人失牙。白介素-10（IL-10）是一种重要的抗炎和免疫抑制细胞因子，在控制炎症和调节获得性免疫应答中具有重要作用。本课题前期研究显示：牙龈卟啉单胞菌脂多糖（P.g LPS）处理在小鼠体内无法有效诱导树突状细胞和自然杀伤细胞的活化，却可明显提高IL-10的表达。故而我们提出假说：牙龈卟啉单胞菌入侵机体初期高表达的IL-10可能是其逃避宿主免疫应答的关键因素之一。因此，采用流式细胞术和细胞分选等技术在小鼠体内探究P.g LPS诱导体内IL-10生成的细胞类型，并利用已有基因敲除小鼠（TLR-2-/-、TLR-4-/-和MyD88-/-）对与IL-10表达细胞相关的受体进行研究，最终在牙周炎小鼠模型中对IL-10表达细胞在清除病原体过程中的作用进行评估，为揭示牙龈卟啉单胞菌入侵牙周初期的免疫机制研究奠定基础。