Oral Pathogens and Dendritic Cell Subsets

口腔病原体和树突状细胞亚群

• 批准号: 7479959
• 负责人: CHRISTOPHER William CUTLER
• 金额: $ 1.4万
• 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 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479959
• 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; Fimbria of hippocampus; 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; Pilum; Play; Pneumonia; Porphyromonas gingivalis; Preparation; Process; Publishing; Regulation; Role; Route; Sentinel; Signal Transduction; Skin; Small Interfering RNA; Staging; Structure-Activity Relationship; T cell regulation; T-Lymphocyte; T-Lymphocyte Subsets; Tissues; Toll-like receptors; Translating; Virus; bone loss; cytokine; human wyatt protein; immune function; immunoregulation; lymph nodes; member; microbial; monocyte; mouse wyatt protein; 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细菌入侵 和病毒。在其不成熟阶段，DC 具有独特的捕获抗原 (Ag) 的能力，表达大量抗原 多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。成熟的 DC 是最有效的 Ag 呈递细胞 (APC)，也是唯一能够刺激初始 T 细胞的 APC。 树突状细胞亚群在慢性牙周炎（CP）中的作用；然而，在此之前基本上不为人所知 这些资助的研究。我们的实验室迄今为止已发表了 11 篇论文，其中 3 篇正在准备中，可归功于 这个 R01，于 2005 年 11 月分娩。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) 中的作用 成熟的 DC 与牙龈固有层中的 CD4+ T 细胞结合。中的主要 DC CP 中的牙龈固有层是表达 DC 特异性 ICAM-3 的那些，该 ICAM-3 抓取非整合素阳性（DC- 签名）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 HIV-1、幽门螺杆菌等主要人类病原体用作“逃逸机制” 肺炎克雷氏菌、结核分枝杆菌、皮法诺利什曼原虫和白色念珠菌。病原体的核心特征 DC-SIGN 的目标是它们会导致持续一生的感染（即 CP），其次， 这些病原体对 Th1 与 Th2 平衡的操纵是其持久存在的核心。我们有 有证据表明 Pg 及其 PAMP 可能靶向 DC 上的 C 型凝集素受体并操纵 Th1-Th2 平衡;我们推测这与 Pg 在口腔粘膜中的持久存在有关。这些建议 因此，继续研究将集中于 C 型凝集素和其他模式识别受体的作用 (PRR) 对 Pg、其 PAMP 的摄取/识别以及 MDDC 的细胞内路由以及其如何调节 适应性免疫反应，特别是 T 调节细胞的诱导。