Ontogenic Programming of Gingival Tissues and Risk of Periodontitis

标题：牙龈组织的个体发育规划和牙周炎的风险 这项建议将集中在使用一个完善的非人灵长类动物（猕猴）模型的口腔 感染，炎症和疾病，是长期合作研究的延续 关系表型可塑性是基因型的一个普遍属性，它指的是同一组基因在同一个基因组中， 当暴露在不同的环境条件下时，基因的多样性可以产生不同的表型结果。这 该项目将提供关于口腔免疫系统的新信息，以及在口腔免疫早期可能发生的变化。 使用宿主模型开发针对常驻微生物组的口腔粘膜免疫设备， 粘膜表面的细菌相互作用。实验设计将解决具体的知识差距 关于口腔微生物组的获得和成熟，以及免疫系统的个体发育， 系统在粘膜表面。提案中的两个范式转变概念是： (1)早期获得的口腔微生物组通常通过母体传播， 年轻个体的牙龈组织反应以及宿主转录组和微生物组的模式将 确定了一个增强的风险概况，特别是与假定的口腔病原体负担增加有关; 和 (2)早期获得也改变了免疫/炎症反应程序， 在诱发性疾病模型中，牙周炎的临床特征增加，即使在来自 牙周炎易感家族 一般假设是“特定免疫应答概况的发展，在口服免疫应答中表达， 粘膜组织，是由早期获得的微生物组的特征调节，”并将进行测试， 通过2个具体目标：具体目标1：描绘健康人中局部免疫基因表达谱 来自与获得性口腔微生物组相关的年轻非人灵长类动物的牙龈组织， 假设：年轻个体牙龈组织中的免疫应答基因表达谱将 这些差异与早期获得性口腔微生物组的特征有关。具体目标2：记录 早期获得性口腔微生物组诱导粘膜免疫应答发育和激活的影响 实验诱导的炎症和牙周炎，将测试假设： 牙周炎会引起免疫反应基因的轮廓，标志着疾病的过程，这些将 与早期获得的口腔微生物组有关。很少有证据表明， 生态学中与个体内宿主反应相互作用的寄生菌和致病菌 牙龈免疫反应系统的发展。这一提议的科学前提是， 口腔微生物组的早期获得和粘膜免疫应答的编程中的变化 反映了牙周炎的家族风险。

Title: Ontogenic Programming of Gingival Tissues and Risk of Periodontitis This proposal will focus on the use of a well-established nonhuman primate (Macaca mulatta) model of oral infection, inflammation, and disease and is a continuation of a long standing collaborative research relationship. Phenotype plasticity is a general attribute of genotypes, and it refers to the fact that the same set of genes can yield different phenotypic outcomes when exposed to distinct environmental conditions. This project will provide novel information on the oral immune system and changes that may occur early in the development of the oral mucosal immune armamentarium to the resident microbiome using a model of host- bacterial interactions at mucosal surfaces. The experimental design will address specific knowledge gaps about the acquisition and maturation of the oral microbiome in conjunction with the ontogeny of the immune system at a mucosal surface. The 2 paradigm shifting concepts in the proposal are: (1) the early acquired oral microbiome, generally transmitted maternally, will “program” the characteristics of gingival tissue responses in younger individuals and patterns of host transcriptome and microbiome will emerge defining an enhanced risk profile particularly related to an increased burden of putative oral pathogens; and (2) the early acquisition also alters immune/inflammatory response programming that will result in increased clinical features of periodontitis in an induced disease model even in younger individuals from periodontitis-susceptible families. The General Hypothesis is that “Development of specific immune response profiles, expressed in the oral mucosal tissues, is regulated by the characteristics of the early acquired microbiome,” and will be tested through 2 specific aims: Specific Aim 1: To delineate profiles of local immune gene expression in healthy gingival tissues derived from young nonhuman primates related to the acquired oral microbiome focusing on the Hypothesis: The immune response gene expression profiles in gingival tissues of young individuals will differ related to the characteristics of the early acquired oral microbiome. Specific Aim 2: To document the impact of early acquired oral microbiome-induced development and activation of mucosal immune responses on experimentally induced inflammation and periodontitis that will test the Hypothesis: Induction of progressing periodontitis will elicit a profile of immune response genes that hallmark the disease process, and these will differ related to the early acquired oral microbiome. There is sparse evidence of the dynamics of acquisition of commensal and pathogenic bacteria in the ecology interfacing with the intra-individual host responses in the development of the gingival immune response system. The scientific premise of this proposal is that variations in the early acquisition of the oral microbiome and programming of the mucosal immune responses are reflective of familial risk for periodontitis.