Oral Pathogens and Dendritic Cell Subsets

描述（由申请人提供）：树突状细胞（dc）是皮肤和粘膜的“哨兵”，在这些组织中巡逻，以防止入侵的细菌和病毒。在其未成熟阶段，dc具有独特的抗原（Ag）捕获能力，表达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淋巴结时，dc下调银捕获受体并上调银呈递受体。成熟的dc是最有效的ag -递呈细胞（apc），也是唯一能够刺激幼稚T细胞的apc。树突状细胞亚群在慢性牙周炎中的作用然而，在这些资助的研究之前，很大程度上是未知的。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2005年11月的R01。我们的研究已经确定了牙龈未成熟DC在原位和体外对牙龈卟啉单胞菌（Pg）的识别和摄取以及成熟DC在牙龈固有层与CD4+ T细胞结合的重要作用。CP牙龈固有层中的主要DC是那些在CP中表达DC特异性ICAM-3攫取非整合素阳性（DC- SIGN）的DC。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、肺炎克雷伯菌、结核分枝杆菌、皮利什曼原虫和白色念珠菌等主要人类病原体用作“逃逸机制”。针对DC-SIGN的病原体的一个核心特征是它们引起的感染可以持续一生（例如CP），其次，这些病原体对Th1-和th2平衡的操纵是其持久性的核心。我们有证据表明Pg及其PAMPs可能靶向dc上的c型凝集素受体并操纵Th1-Th2平衡；我们认为这与Pg在口腔黏膜的持续存在有关。因此，这些持续的研究将集中在c型凝集素和其他模式识别受体（PRR）在Pg及其PAMPs的摄取/识别和mddc的细胞内通路中的作用，以及这如何调节适应性免疫反应，特别是T调节性细胞的诱导。

DESCRIPTION (provided by applicant): 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-integrin-positive (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, Klebsiella 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 second, 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 posit 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.