Oral Pathogens and Dendritic Cell Subsets

描述(改编自《调查员摘要》)：负责人 研究人员提出了一种新的总体假设和方法 了解成人牙周炎(AP)的病理生理学 一种折磨美国民众的常见疾病。而美国人的死亡率 牙列是AP最常见的结局，其与其他疾病的联系更为严重 疾病，包括冠状动脉疾病、呼吸系统疾病和早产儿 劳动不能被忽视。这些调查人员呼吁人们注意到许多 AP和接触性过敏症(CHS)之间有趣的相似之处。CHS是 是困扰人类的最常见的皮肤病之一，也是 对体内免疫反应进行了深入研究。AP和CHS都针对 宿主被膜(牙龈或皮肤)，并且似乎涉及到激活和 抗原捕获和提呈细胞的相似亚群的致敏作用 树突状细胞。树突状细胞被称为“大自然的佐剂”， 在抗原提呈方面比巨噬细胞或B细胞更有效，而且唯一的 抗原提呈细胞(APC)可以刺激原始T细胞 扩散。这种免疫刺激能力也可能产生有害的影响。 对宿主来说，以接触超敏反应(CHS)为代表。两个AP CHS涉及一种主要由两者介导的破坏性T细胞反应 调节性和效应性T细胞。这些调查人员已经证明 牙龈卟啉单胞菌在这方面是一种独特的病原体，能够感染， 在体外和可能的原位敏化和激活树突状细胞。许多 关于牙龈假单胞菌致敏的树突状细胞在AP中作用的问题， 然而，仍未得到答复。本提案将最终确立， 采用原位、体外和体外方法，树突状细胞在 成人牙周炎，尤其是由牙周炎引起的牙周炎。此外， 这些研究将描述牙龈假单胞菌与 并将进一步加深我们对AP AS病理生理学的认识 它与CHS有关。未来的研究，在这项提议的范围之外，将 了解T细胞对牙龈假单胞菌激活的树突状细胞的反应 细胞。

DESCRIPTION (Adapted from the Investigator's Abstract): The Principal Investigator has proposed a novel overall hypothesis and approach to understanding the pathophysiology of adult periodontitis (AP), one of the most common of diseases that afflict the US population. While mortality of the dentition is the most familiar outcome of AP, its links with other more severe diseases, including coronary artery disease, respiratory diseases and pre-term labor cannot be ignored. These investigators have called attention to the many intriguing parallels between AP and contact hypersensitivity (CHS). CHS is among the most common of dermatoses that afflicts mankind and one of the most intensively studied of in vivo immune responses. Both AP and CHS target the host integument (gingiva or skin) and appear to involve the activation and sensitization of similar subsets of antigen capture and presenting cells, the dendritic cells. Dendritic cells have been termed "Nature's adjuvant," being more efficient at antigen-presentation than macrophages or B cells and the only antigen-presenting cells (APCs) than can stimulate naive T cells to proliferate. This immunostimulatory capacity can also have detrimental effects for the host, as typified by contact hypersensitivity (CHS) responses. Both AP and CHS involve a predominantly destructive T cell response mediated by both regulatory and effector T cells. These investigators have shown that Porphyromonas gingivalis is a unique pathogen in this regard, able to infect, sensitize, and activate dendritic cells in vitro and likely, in situ. Many questions about the role of P. gingivalis-sensitized dendritic cells in AP, however, remain unanswered. The present proposal will definitively establish, using in situ, ex vivo and in vitro approaches, the role of dendritic cells in adult periodontitis, particularly that induced by P. gingivalis. Moreover, these studies will characterize the interactions of P. gingivalis with dendritic cells and will further our knowledge of the pathophysiology of AP as it relates to CHS. Future studies, outside the purview of this proposal, will involve understanding the T cell response to P. gingivalis-activated dendritic cells.