LBP/CD14 interactions with bacterial components

描述（申请人摘要中的逐字描述）：先天性宿主炎性 反应机制通常防止微生物感染。落入临床 健康牙周组织，低水平表达选择的炎症介质， 被观察到，并被认为提供炎症监测，保护 这个组织经常暴露在细菌中。在牙周炎中， 破坏牙根表面周围的组织和骨骼， 这种疾病的特征被认为是由于高水平表达 许多先天性宿主炎症介质。与开发相关 成人型牙周炎是最常见的疾病， 牙菌斑生物膜植物群的特征性转变， 主要是革兰氏阴性细菌。与疾病的临床相关性 与这种转变相关的是强大的，然而，不知道这些是如何实现的。 细菌种群的变化影响炎症反应。LBP / CD 14/ Toll样受体（TLR）系统已显示促进先天性宿主免疫应答。 对各种不同细菌的炎症反应。这些关键 先天性宿主防御蛋白对来自革兰氏阳性生物的两种LTA都有应答 和来自革兰氏阴性菌的LPS。有证据表明，CD 14和TLR可能起作用 共同调节炎症介质产生的强度， 对不同细菌的反应。CD 14与多种不同的 微生物配体有效地浓缩它们并将它们“呈现”给其他微生物。 先天宿主防御成分如TLR。相反，不同的TLR 与不同的微生物配体结合，导致宿主的活化 细胞反应。然而，CD 14识别的分子机制 许多不同的细菌成分和特定的 LPS或LTA与CD 14或TLR相互作用的结构特征不 完全理解我们的总体假设是：先天宿主防御 系统识别细菌的部分结构特征存在于 脂多糖（LPS）和脂磷壁酸（LTA），并调节 相应的炎症反应。在本提案中， 影响CD 14和TLR结合和活化的LPS和LTA将被抑制。 考察我们将确定特定的CD 14残基在LPS和LTA中的作用， 与TLR-2和TLR-4结合并转移，并确定TLR-2和TLR-4的贡献 TLR-2和TLR-4对宿主细胞活化具有不同的结构定义 微生物配体这些研究将进一步深入了解 先天宿主防御系统识别并响应不同的细菌， 口腔健康和疾病的组成部分。

DESCRIPTION (Verbatim from Applicant's Abstract): Innate host inflammatory response mechanisms normally prevent microbial infection. In the clinically healthy periodontium, low level expression of select inflammatory mediators has been observed and is believed to provide inflammatory surveillance, protecting this tissue which is constantly exposed to bacteria. In periodontitis, the destruction of the tissue and bone surrounding the tooth root surface which is characteristic of this disease is believed to be due to high level expression of numerous innate host inflammatory mediators. Associated with the development of adult type periodontitis, the most common form of the disease, there is a characteristic shift in the dental plaque biofilm flora from mostly gram positive to mostly gram negative bacteria. The clinical correlation to disease associated with this shift is strong, however, it is not understood how these bacterial population changes influence the inflammatory response. The LBP / CD14 / Toll like receptor (TLR) system has been shown to facilitate innate host inflammatory responses to a wide variety of different bacteria. These key innate host defense proteins respond to both LTA from gram positive organisms and LPS from gram negative bacteria. Evidence suggests CD14 and TLR's may act together in regulating the intensity of inflammatory mediator production in response to different bacteria. CD14 interacts with a wide variety of different microbial ligands effectively concentrating them and "presenting" them to other innate host defense components such as TLRs. In contrast different TLRs are engaged with different microbial ligands resulting in activation of host cellular responses. However, the molecular mechanisms by which CD14 recognizes numerous different bacterial components and the contribution of specific structural features of LPS or LTA to CD14 or TLR interactions are not completely understood. Our overall hypothesis is: The innate host defense system recognizes bacteria in part by structural features present on lipopolysaccharide (LPS) and lipoteichoic acid (LTA) and modulates the inflammatory response accordingly. In this proposal, the structural features of LPS and LTA that influence CD14 and TLR binding and activation will be examined. We will determine the role of specific CD14 residues in LPS and LTA binding and transfer to TLR-2 and TLR-4, and determine the contribution of TLR-2 and TLR-4 to host cell activation with different structurally defined microbial ligands. These studies will provide further insight into how the innate host defense system recognizes and responds to different bacteria, a key component of both oral health and disease.