Microbial nucleic acid sensing in periodontitis

 描述(申请人提供)：微生物核酸代表一组微生物相关的分子模式，通过触发炎症反应的细胞内固有传感器识别。Toll样受体9(TLR9)是微生物DNA的主要受体。利用反向翻译的方法，我们发现TLR9通过加剧局部炎症反应参与了牙周病的发病。目前的提案将扩展我们之前的研究，以充分表征TLR9在牙周炎中触发炎症的生物学途径和细胞来源。我们将确定TLR9与其他与牙周炎有关的先天感受器的非冗余和协同作用。TLR9抑制剂对牙周病预后的影响也将被评估。牙周病不仅局限于牙龈组织，还与各种系统性疾病有关。对远距离牙周微生物DNA的鉴定表明，微生物核酸传感可能不仅在牙周病的发病机制中起重要作用，而且还可能导致牙周病对全身健康的不利影响。因此，建议的研究不仅将确定控制局部持续性牙周炎的新的生物学途径和治疗靶点，而且还将导致未来的研究。 确定牙周炎和全身并发症之间的新联系。

 DESCRIPTION (provided by applicant): Microbial nucleic acids represent a group of microbe-associated molecular patterns that are recognized through intracellular innate sensors triggering inflammatory responses. Toll like receptor 9 (TLR9) is the major receptor for microbial DNA. Using a reverse translational approach, we revealed that TLR9 contributes to periodontal disease pathogenesis through exacerbating the local inflammatory responses. Current proposal will extend our previous studies to fully characterize the biological pathways and cellular sources of TLR9-triggered inflammation in periodontitis. We will determine both the non-redundant as well as cooperative role of TLR9 with other innate sensors implicated in periodontitis. The effect of TLR9 inhibitors to periodontal disease outcome will also be evaluated. Periodontal disease is not only limited to gingival tissues but also is associated with various systemic diseases. Identification of periodontal microbial DNA at distant sites suggests that microbial nucleic acid sensing may not be only important in periodontal disease pathogenesis but also contributes to periodontal disease adverse effects on systemic health. Therefore, the proposed studies will not only identify novel biological pathways and therapeutic targets to control local persistent periodontal inflammation but also lead to future investigations to identify a novel link between periodontitis and systemic complications.