Oral Pathogens and Dendritic Cell Subsets

口腔病原体和树突状细胞亚群

• 批准号: 6411298
• 负责人: CHRISTOPHER William CUTLER
• 金额: $ 28.33万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6411298
• 关键词: Bacteroides gingivalis; T lymphocyte; bacteria infection mechanism; bacterial antigens; biopsy; cellular immunity; confocal scanning microscopy; contact dermatitis; cytokine; dendritic cells; epithelium; flow cytometry; gingiva; human subject; human tissue; humoral immunity; immunofluorescence technique; messenger RNA; oral bacteria; periodontitis; phagocytosis; phenotype; polymerase chain reaction; stainings; tissue /cell culture

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.

描述（改编自研究者摘要）：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， 这是困扰美国人口的常见疾病。虽然死亡率 牙列是AP最常见的结果，它与其他更严重的疾病有关。 疾病，包括冠状动脉疾病、呼吸系统疾病和早产儿 劳动力不容忽视。这些调查人员已经引起了许多人的注意， AP和接触性超敏反应（CHS）之间有趣的相似之处。CHS是 其中最常见的皮肤病，折磨人类和一个最 深入研究体内免疫反应。AP和CHS都针对 宿主外皮（牙龈或皮肤），似乎涉及激活， 抗原捕获和呈递细胞的相似亚群的致敏， 树突状细胞树突状细胞被称为“天然佐剂”， 比巨噬细胞或B细胞更有效地呈递抗原， 抗原呈递细胞（APC），可以刺激幼稚T细胞， 增殖。这种免疫刺激能力也可能产生有害影响 对宿主而言，以接触性超敏反应（CHS）为代表。两部AP CHS和CHS涉及由两者介导的主要破坏性T细胞应答， 调节和效应T细胞。这些调查人员已经表明， 牙龈卟啉单胞菌在这方面是一种独特的病原体，能够感染， 致敏，并激活树突状细胞在体外和可能，在原位。许多 关于牙龈卟啉单胞菌致敏的树突状细胞在AP中的作用的问题， 但仍没有得到答复。本提案将明确规定， 使用原位、离体和体外方法，树突状细胞在 成人牙周炎，特别是牙龈卟啉单胞菌引起的牙周炎。此外，委员会认为， 这些研究将描述牙龈卟啉单胞菌与 树突状细胞，并将进一步我们的知识，病理生理学的AP， 它与CHS有关。本建议范围以外的未来研究将 包括理解T细胞对牙龈卟啉单胞菌激活的树突状细胞的反应， 细胞