ONTOGENY OF INNATE IMMUNE RESPONSES AT MUCOSAL SURFACES

粘膜表面先天免疫反应的个体发生

• 批准号: 8360732
• 负责人: Octavio Alberto Gonzalez
• 金额: $ 48.72万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360732
• 关键词: Address; Age; Animals; Blood Circulation; Caribbean region; Characteristics; Controlled Study; Cross-Sectional Studies; Dental Schools; Development; Disease; Equilibrium; Event; Funding; Gene Expression; Gingiva; Grant; Growth; Homeostasis; Human; Immune; Immune response; Immune system; Individual; Infection; Inflammation; Kentucky; Macaca mulatta; Modeling; Molecular; National Center for Research Resources; Natural Immunity; Oral; Oral cavity; Periodontal Diseases; Periodontal Infection; Periodontitis; Play; Primates; Principal Investigator; Process; Puerto Rico; Reaction; Research; Research Infrastructure; Research Personnel; Resolution; Resources; Role; Source; Surface; System; Systemic disease; Technology; Tissues; United States National Institutes of Health; Universities; aged; base; cohort; cost; innovation; microbial; nonhuman primate; novel; oral infection; receptor; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The hallmark of the vertebrate immune system is its ability to maintain an equilibrium between reactivity and quiescence of responses, while geared to respond and adapt rapidly to noxious and potentially lethal challenge. The system must recognize the challenge, develop and express a response to control the challenge, and terminate the reaction in regulating the response. These reactions are the responsibility of components of innate immunity that include cellular receptors and biomolecules at mucosal surfaces and within the systemic circulation. Due to the complexity of the microbial challenge in the oral cavity, it is clear that the innate immune system must play a crucial role in regulating host responses to the commensal microbiota. This proposal engages a collaborative relationship to enable determination of these responses in a human-like model of oral infection and inflammation: (1) This proposal will focus on the use of a nonhuman primate (rhesus) model of periodontal infection and inflammation. It is built upon a unique resource, the Caribbean Primate Research Center (CPRC); (2) This proposal is a collaborative relationship between investigators at the University of Kentucky, the CPRC, and the University of Puerto Rico Dental School; (3) This proposal will provide novel information on innate immunity in cross-sectional studies related to age using various cohorts from young to aged animals, and related to the expression of periodontitis; and, (4) Using the nonhuman primate model of periodontal infection and disease, we will determine longitudinal changes in innate immune responses througout age of development of the individual, specifically related to the initiation, progression, and resolution of the disease process. This model provides for a controlled study of these processes that cannot be accomplished in humans, but provides a human-like model of infection, disease and host responses. The General Hypothesis for the project is that "Innate immune response components in gingival tissues vary with age and periodontal disease expression." This will enable the identification of crucial innate immune molecular events that contribute to gingival homeostasis. The studies proposed in this application will use an innovative strategy in 2 Specific Aims to interface a nonhuman primate model of periodontitis, with microarray gene expression technology to address these critical questions regarding the characteristics and ontogeny of innate responses in the oral cavity.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 脊椎动物免疫系统的标志是其能够维持反应的反应性和静止性之间的平衡，同时能够快速响应和适应有害和潜在致命的挑战。 系统必须识别挑战，制定并表达响应以控制挑战，并在调节响应时终止反应。 这些反应是先天免疫组成部分的责任，包括粘膜表面和体循环内的细胞受体和生物分子。 由于口腔中微生物挑战的复杂性，很明显，先天免疫系统在调节宿主对共生微生物群的反应中必须发挥至关重要的作用。 该提案建立了合作关系，以便能够在口腔感染和炎症的类人模型中确定这些反应：（1）该提案将重点关注牙周感染和炎症的非人类灵长类动物（恒河猴）模型的使用。它建立在独特的资源之上，即加勒比灵长类动物研究中心（CPRC）； (2) 该提案是肯塔基大学、CPRC 和波多黎各大学牙科学院研究人员之间的合作关系； (3) 该提案将在使用从年轻到老年动物的各种队列进行的与年龄相关的横断面研究中提供关于先天免疫的新信息，以及与牙周炎的表达相关的信息； (4)利用牙周感染和疾病的非人类灵长类动物模型，我们将确定先天免疫反应在个体发育过程中的纵向变化，特别是与疾病过程的起始、进展和消退相关的变化。 该模型提供了对人类无法完成的这些过程的对照研究，但提供了感染、疾病和宿主反应的类人模型。该项目的一般假设是“牙龈组织中的先天免疫反应成分随年龄和牙周病表现而变化”。 这将能够识别有助于牙龈稳态的关键先天免疫分子事件。本申请中提出的研究将使用 2 个具体目标中的创新策略来连接非人类灵长类动物牙周炎模型，并通过微阵列基因表达技术来解决有关口腔先天反应的特征和个体发育的关键问题。