Oral Pathogens and Dendritic Cell Subsets

口腔病原体和树突状细胞亚群

• 批准号: 7743442
• 负责人: CHRISTOPHER William CUTLER
• 金额: $ 35.74万
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7743442
• 关键词: Address; Antigens; B-Lymphocytes; Bacteria; Bacterial Infections; C Type Lectin Receptors; C-Type Lectins; CD4 Positive T Lymphocytes; Candida albicans; Carbohydrates; Cell Line; Cell Maturation; Cells; Dendritic Cells; Dermal; Disease; Epithelium; Equilibrium; Event; Family; Funding; Genetic Transcription; Gingiva; Goals; HIV-1; Helicobacter pylori; Human; Immune; Immune Cell Activation; Immune Tolerance; Immune response; Immune system; Immunity; Immunosuppressive Agents; Immunotherapy; In Situ; In Vitro; Infection; Invaded; Knowledge; Lamina Propria; Lectin; Leishmania; Ligands; Lymphocyte antigen CD50; Mediating; Mediator of activation protein; Molecular; Monitor; Mucous Membrane; Mycobacterium tuberculosis; Myelogenous; Oral; Oral mucous membrane structure; Osteoclasts; Paper; Pathogenesis; Pattern; Pattern recognition receptor; Periodontitis; Play; Pneumonia; Porphyromonas gingivalis; Preparation; Process; Publishing; Regulation; Regulatory T-Lymphocyte; Role; Route; Sentinel; Signal Transduction; Skin; Small Interfering RNA; Staging; Structure-Activity Relationship; T cell regulation; T cell response; T-Lymphocyte; T-Lymphocyte Subsets; Tissues; Toll-like receptors; Translating; Virus; adaptive immunity; bone loss; cytokine; fimbria; immunoregulation; innate immune function; lymph nodes; member; microbial; monocyte; oral pathogen; pathogen; progenitor; receptor; response; scavenger receptor; soft tissue; uptake

Dendritic cells (DCs) are the "sentinels" of the skin and mucosa, patrolling these tissues for invading bacteria and viruses. In their immature stage, DCs are uniquely equipped for antigen (Ag) capture, expressing a large variety of scavenger receptors and other pattern recognition receptors. As they mature and migrate to the lymph nodes, DCs downregulate Ag-capture receptors and upregulate Ag-presenting receptors. Mature DCs are the most efficient Ag-presenting cells (APCs), and the only APCs capable of stimulating naive T cells. The role of dendritic cell subpopulations in chronic periodontitis (CP); however, was largely unknown prior to these funded studies. Our lab has thus far published 11 papers, with 3 in preparation that can be credited to this R01, which terms in November of 2005. Our studies have identified an important role for gingival immature DC in the recognition and uptake of Porphyromonas gingivalis (Pg) in situ and in vitro, and for maturing DCs in engagement with CD4+ T cells in the gingival lamina propria. The principle DCs in the gingival lamina propria in CP are those that express DC-specific ICAM-3 grabbing non-integrinpositive (DC- SIGN) in CP. DC-SIGN is a member of a family of C-type lectins; it is a type II transmembrane receptor that is used as an "escape mechanism" by major human pathogens including HIV-1, Helicobacter pylori, Klepsiella pneumonia, M tuberculosis, Leishmania pifanoi and C albicans. A central feature of pathogens that target DC-SIGN is that they cause infections that can last a lifetime (i.e. such as CP) and secondly, that manipulation of the Th1- versus Th2-balance by these pathogens is central to their persistence. We have evidence that Pg and its PAMPs may target C-type lectin receptors on DCs and manipulate the Th1-Th2 balance; we hypothesize that this is involved in persistence of Pg in the oral mucosa. These proposed continued studies will therefore focus on the role of C-type lectins and other pattern recognition receptors (PRR) in uptake/recognition of Pg, its PAMPs and in intracellular routing by MDDCs and how this modulates the adaptive immune response, in particular, the induction of T regulatory cells.

树突状细胞（DC）是皮肤和粘膜的“哨兵”，巡逻这些组织以防止入侵细菌 和病毒。在它们的未成熟阶段，DC独特地装备用于抗原（Ag）捕获，表达大的 各种清道夫受体和其他模式识别受体。当它们成熟并迁移到 在淋巴结中，DC下调Ag捕获受体并上调Ag呈递受体。成熟dc 是最有效的Ag呈递细胞（APCs），并且是唯一能够刺激幼稚T细胞的APCs。 然而，树突状细胞亚群在慢性牙周炎（CP）中的作用在很大程度上是未知的， 这些资助的研究。到目前为止，我们的实验室已经发表了11篇论文，其中3篇正在准备中，可以归功于 这个R 01，在2005年11月到期。我们的研究已经确定了牙龈的重要作用， 未成熟DC在原位和体外识别和摄取牙龈卟啉单胞菌（Pg）， 成熟的DC与牙龈固有层中的CD 4 + T细胞接合。主要的发展中国家 CP中的牙龈固有层是表达DC特异性ICAM-3抓取非整合素阳性（DC-1）的那些。 在CP中。DC-SIGN是C型凝集素家族的成员;它是一种II型跨膜受体， 被主要的人类病原体，包括HIV-1，幽门螺杆菌， 肺炎克雷伯氏菌、结核分枝杆菌、皮凡利什曼原虫和白色念珠菌。病原体的一个核心特征 靶向DC-SIGN的是，它们引起的感染可以持续一生（即，如CP），其次， 这些病原体对Th 1-对Th 2-平衡的操纵是其持续存在的关键。我们有 Pg及其PAMPs可能靶向DC上的C型凝集素受体，并操纵Th 1-Th 2 平衡;我们假设这与口腔粘膜中Pg的持久性有关。这些拟议 因此，继续的研究将集中在C型凝集素和其他模式识别受体的作用上 (PRR)在Pg、其PAMP的摄取/识别中以及在MDDC的细胞内路由中以及这如何调节 适应性免疫应答，特别是调节性T细胞的诱导。