Genomics Periodontal Host-Parasite Interactions

描述（由申请人提供）：牙周炎是一种炎症性疾病，已知宿主-寄生虫相互作用有助于结缔组织破坏和牙槽骨吸收，这是牙周炎的标志。牙龈卟啉单胞菌（p.g.）是一种黑色革兰氏阴性厌氧菌，在牙周病的发生和发展中被认为是一种主要的牙周病原体。其细菌细胞壁和附属物上的结构，如脂多糖（LPS）和菌毛，在诱导先天免疫应答中发挥重要作用，包括局部和循环白细胞（如单核细胞/巨噬细胞）产生细胞因子。根据我们的初步数据，我们假设活的P.g.刺激了人类PBM中独特的促炎信号转导途径，而不是纯化的细菌成分，如P.g. LPS或P.g.原纤维。为了验证这一点，提出了以下具体目标：目的1：在转录水平上验证人类外周血单核细胞中活的P.g.、P.g. LPS和P.g.菌毛诱导独特信号通路的假设。目的2：在蛋白表达水平上验证活的P.g.、P.g. LPS和P.g.纤维在人PBM中不同诱导的独特信号通路的假设。目标3：为了确定目标1和目标2中确定的独特信号通路的功能意义，我们将在体外和体内对其进行测试。这些研究结果将为我们了解牙周病的病因和发病机制提供一个新的途径。由于在我们的初步数据中确定的不同宿主先天反应实际上可能代表牙周感染的不同阶段，因此该结果有望具有重要的治疗意义。

DESCRIPTION (provided by applicant): Periodontitis is an inflammatory disease with host-parasite interactions known to contribute to connective tissue destruction and alveolar bone resorption the landmark of this disease. Porphyromonas gingivalis (P.g.), a black-pigmented Gram-negative anaerobic bacterium, has been implicated as a major periodontal pathogen in the development and progression of periodontal disease. Structures on its bacterial cell wall and appendage, such as lipopolysaccharide (LPS) and fimbriae, play important roles in the induction of innate immune responses, including cytokine production by localized and circulating leukocytes, such as monocyte/macrophage. Based on our preliminary data, we hypothesize that live P.g. stimulates unique pro-inflammatory signal transduction pathways in human PBM as opposed to purified bacterial components, such as P.g. LPS or P.g. fimbriac. To test this, the following specific aims are proposed: Aim 1: To test at the transcriptional level the hypothesis that unique signaling pathways are differentially induced by live P.g., P.g. LPS and P.g. fimbriae in human peripheral blood monocytes. Aim 2: To test at the level of protein expression the hypothesis that unique signaling pathways are differentially induced by live P.g., P.g. LPS and P.g. fimbriac in human PBM. Aim 3: To establish the functional significance of unique signaling pathways identified in Aims 1 and 2 we will test them in vitro and in vivo. The results of these studies should provide a new gateway to our understanding of the etiology and pathogenesis of periodontal diseases. Since the differential host innate response identified in our preliminary data may in fact represent different stages of the periodontal infection, the results are expected to have important therapeutic implications.