Oral Pathogens and Dendritic Cell Subsets

树突状细胞(DC)是皮肤和粘膜的“哨兵”，在这些组织中巡逻，寻找入侵的细菌。 和病毒。在其未成熟阶段，DC具有捕获抗原(Ag)的独特装备，表达大量的 各种清道夫受体和其他模式识别受体。随着他们的成熟和迁移到 在淋巴结中，树突状细胞下调抗原捕获受体，上调抗原呈递受体。成熟的区议会 是最有效的抗原提呈细胞，也是唯一能够刺激幼稚T细胞的抗原提呈细胞。 树突状细胞亚群在慢性牙周炎中的作用；然而，在此之前，人们对此知之甚少。 这些资助的研究。到目前为止，我们实验室已经发表了11篇论文，其中3篇正在准备中，这归功于 本R01，条款为2005年11月。我们的研究已经确定了牙龈的一个重要作用 未成熟DC对牙龈卟啉单胞菌(Pg)的识别和摄取 成熟的DC与牙周固有层中的CD4T细胞结合。区议会的原则 CP的牙周固有层是表达DC特异性的ICAM-3抓取非整合素阳性(DC- 在CP中签名)。DC-SIGN是C型凝集素家族的一员；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、皮氏利什曼原虫和白色念珠菌。病原体的一个中心特征 目标DC-SIGN是它们引起可持续终生的感染(如CP)，其次， 这些病原体对Th1和Th2平衡的操纵是它们持续存在的核心。我们有 PG及其PAMPs靶向DC表面C型凝集素受体并调控Th1-Th2的证据 平衡；我们假设这与口腔粘膜中PG的持久性有关。这些建议 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 (PRR)在PG及其PAMPs的摄取/识别和MDDC的细胞内路由中的作用及其调节 获得性免疫反应，特别是T调节细胞的诱导。

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.