ONTOGENY OF INNATE IMMUNE RESPONSES AT MUCOSAL SURFACES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 脊椎动物免疫系统的特点是它有能力在反应活跃和反应静止之间保持平衡，同时准备对有害的和潜在的致命挑战做出快速反应和适应。系统必须识别挑战，制定并表达控制挑战的反应，并在调节反应中终止反应。这些反应是先天免疫的组成部分负责的，包括粘膜表面和体循环中的细胞受体和生物分子。由于口腔微生物挑战的复杂性，很明显，天然免疫系统必须在调节宿主对共生微生物区系的反应中发挥关键作用。这项建议采用合作关系，以便能够在类似人类的口腔感染和炎症模型中确定这些反应：(1)这项建议将重点放在使用非人类灵长类动物(恒河猴)的牙周感染和炎症模型。它建立在一个独特的资源--加勒比灵长类动物研究中心(CPRC)的基础上；(2)这项建议是肯塔基大学、CPRC和波多黎各大学牙科学校的研究人员之间的合作关系；(3)这项建议将在与年龄有关的横断面研究中提供新的信息，使用从幼年动物到老年动物的各种队列，并与牙周炎的表达有关；并且，(4)使用牙周感染和疾病的非人类灵长类动物模型，我们将确定个体发育过程中先天免疫反应的纵向变化，特别是与疾病过程的启动、进展和解决有关的变化。这个模型提供了对这些过程的对照研究，这些过程不能在人类身上完成，但提供了一个类似于人类的感染、疾病和宿主反应的模型。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的表现而不同。”这将使关键的先天免疫分子事件的识别有助于牙龈内环境的稳定。在这项申请中提出的研究将在2个具体目标中使用创新策略，将牙周炎的非人类灵长类动物模型与微阵列基因表达技术相结合，以解决关于口腔内天然反应的特征和个体发育的这些关键问题。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.