Oral Commensal Bacterial Modulation of the Periodontal Innate Host Response

说明（由申请人提供）：本申请基于这样的前提，即先天宿主对口腔粘膜定植的反应5对宿主有益。换句话说，宿主对口腔共生细菌定植引起的保护性反应实际上有助于预防疾病的正常牙周组织功能。已知临床上健康的牙周组织含有选择的先天宿主防御组分的高度协调的表达模式，所述先天宿主防御组分被认为在保护该组织和宿主免受病原体侵害中起作用。在无菌小鼠中的研究已经揭示，肠道的肠道细菌定殖刺激宿主反应，这有助于肠道在免疫和组织功能方面的个体发育。因此，我们希望测试假设：“口腔共生菌有助于临床健康牙周组织中发现的先天宿主反应的个体发育”。我们将在三个具体目标中检验这一假设。具体目标1将比较无菌和常规饲养小鼠的牙周先天后防御状态，以确定由牙周口腔细菌调节的宿主成分。这一目的将确定牙周细菌的贡献，在牙周组织的先天宿主反应的个体发育。具体目标2将确定牙龈卟啉单胞菌（一种众所周知的牙周病病原体）是否可以改变宿主与其口腔植物群之间建立的“有益体内平衡”。具体目标3将确定牙龈上皮细胞TLR 2和TLR 4表达水平的变化，其可能改变与宿主的牙龈内稳态。由于微生物组成和先天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，因此最后两个目的可能与口腔细菌/宿主相互作用的改变相关，这种改变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.