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）：本申请基于以下前提：先天主机对口腔共生殖民化5对主机有益。换句话说，宿主对口服共生细菌定植引起的保护反应实际上有助于牙周组织的正常功能，以预防疾病。众所周知，临床健康的牙周组织包含精选的先天宿主防御组件的高度精心策划的表达模式，这些表达模式被认为可以在保护该组织和宿主免受病原体中起作用。在无菌小鼠中的研究表明，肠道的共生细菌定殖刺激了宿主反应，这有助于在免疫和组织功能方面有助于肠的本体发育。因此，我们希望检验以下假设：“共生口服细菌有助于在临床健康牙周组织中发现的先天宿主反应的个体发育”。我们将以三个特定目标来检查这一假设。具体目标1将比较无菌和传统饲养小鼠的牙周先天后防御状况，以识别那些受共生口服细菌调节的宿主成分。该目标将确定共生细菌对牙周恩斯宿主反应的个体发育的贡献。具体的目标2将确定牙疟原虫是否可以改变宿主与其共生菌群之间建立的“有益稳态”。 n特定目标3将确定可能改变与宿主的共生稳态的牙龈上皮细胞TLR2和TLR4表达水平的变化。由于微生物组成和先天宿主的响应表达模式都是动态的，并且可能会随着时间的流逝而改变，因此，最后两个目标可能与口服细菌I宿主相互作用的改变可能随着年龄的增长而发生。