Oral Commensal Bacterial Modulation of the Periodontal Innate Host Response

口腔共生细菌对牙周先天宿主反应的调节

• 批准号: 7463693
• 负责人: Richard Peters Darveau
• 金额: $ 28.52万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-09 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7463693
• 关键词: Age; Animals; Bacteria; Binding; Cell Wall; Epithelial; Epithelial Cells; Fusobacterium nucleatum; Gene Expression Regulation; Genes; Genome; Germ-Free; Gingiva; Growth; Health; Hemin; Histologic; Homeostasis; Host Defense; Immune; Immune response; Immune system; Incubated; Integration Host Factors; Intestines; LTA gene; Life; Lipid A; Mediator of activation protein; Microarray Analysis; Molecular; Mus; Oral; Pattern; Periodontium; Play; Porphyromonas gingivalis; Proteins; Research Personnel; Role; Streptococcus; Streptococcus gordonii; System; TLR2 gene; TLR4 gene; Testing; Time; Tissues; Tumor Necrosis Factor-Beta; base; commensal microbes; disorder prevention; microbial; microbial community; mutant; novel; oral bacteria; oral commensal; pathogen; periopathogen; programs; response

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.

描述（由申请人提供）：本申请基于先天宿主对口腔共生定植的反应对宿主有益的前提。换句话说，宿主对口腔共生细菌定植的保护反应实际上有助于正常的牙周组织功能，从而预防疾病。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，选择先天宿主防御成分，被认为在保护组织和宿主免受病原体侵害方面起作用。无菌小鼠的研究表明，肠道的共生细菌定植刺激宿主反应，促进肠道在免疫和组织功能方面的个体发生。因此，我们希望验证这一假设：“在临床健康的牙周组织中发现的口腔共生细菌有助于先天宿主反应的个体发生”。我们将在三个具体目标中检验这一假设。特异性目的1将比较无菌和常规饲养小鼠的牙周先天后防御状态，以确定由共生口腔细菌调节的宿主成分。这个目的将确定共生细菌的贡献，以牙周组织的先天宿主反应的个体发生。特异性目标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宿主与其共生菌群之间建立的“有益稳态”。n特异性Aim 3将确定牙龈上皮细胞TLR2和TLR4表达水平的变化可能改变与宿主的共生稳态。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，后两个目的可能与口腔细菌I宿主相互作用的改变有关，这种变化可能随着年龄的增长而发生。