Oral Commensal Bacterial Modulation of the Periodontal Innate Host Response

描述(申请人提供)：本申请基于这样一个前提，即先天宿主对口腔共生定居的反应对宿主有利。换句话说，宿主对口腔共生细菌定植的保护性反应实际上有助于在预防疾病方面正常的牙周组织功能。众所周知，临床健康的牙周组织包含一种高度协调的表达模式，这些表达模式选择的固有宿主防御成分被认为具有保护组织和宿主免受病原体侵袭的功能。对无菌小鼠的研究表明，肠道的共生细菌定植刺激宿主反应，在免疫和组织功能方面有助于肠道的个体发育。因此，我们希望验证这样的假设：“口腔共生细菌有助于在临床健康的牙周组织中发现的先天宿主反应的个体发育”。我们将从三个具体目标来检验这一假说。具体目标1将比较无菌小鼠和常规饲养小鼠的牙周先天防御状态，以确定那些受共生口腔细菌调控的宿主成分。这一目标将确定共生细菌对牙周组织内固有宿主反应的个体发育的贡献。具体目标2将确定牙龈假单胞菌，一种众所周知的周围病原体是否可以改变在宿主和其共生菌群之间建立的“有益的动态平衡”。N特定目的3将确定牙龈上皮细胞TLR2和TLR4表达水平的变化，这些变化可能改变与宿主的共生平衡。由于微生物组成和固有宿主反应表达模式都是动态的，并且可能随着时间的推移而改变，最后两个目标可能与口腔细菌I宿主相互作用的变化有关，这种变化可能随着年龄的增长而发生。

DESCRIPTION (provided by applicant): This application is based upon the premise that the innate host response to oral commensal colonization 5 beneficial to the host. In other words, the protective response elicited by the host to oral commensal bacterial colonization in fact contributes to normal periodontal tissue functions with respect to prevention of disease. It is known that clinically healthy periodontal tissue contains a highly orchestrated expression pattern of select innate host defense components that are believed to function in protecting this tissue and the host from pathogens. Studies in germ-free mice have revealed that commensal bacterial colonization of the intestine stimulates host responses that contribute to the ontogeny of the intestine with respect to immune and tissue function. Therefore, we wish to test the hypothesis that: "Commensal oral bacteria contribute to the ontogeny of the innate host response found in clinically healthy periodontal tissue". We will examine this hypothesis in three Specific Aims. Specific Aim 1 will compare the periodontal innate post defense status in germ-free and conventionally reared mice to identify those host components regulated by commensal oral bacteria. This Aim will determine the contribution of commensal bacteria to the ontogeny of the innate host response in the periodontium. Specific Aim 2 will determine if P. gingivalls, a well-known periopathogen can alter the "beneficial homeostasis" established between the host and its commensal flora. n Specific Aim 3 changes in gingival epithelial cell TLR2 and TLR4 expression levels that may alter commensal homeostasis with the host will be determined. Since both microbial composition and innate host response expression patterns are dynamic and likely to change over time these last two Aims are potentially relevant to alterations in oral bacterial I host interactions that may occur with increasing age.