Contribution of oral bacteria to healthy homeostasis

描述(申请人提供)：口腔共生细菌对口腔健康的贡献尚不完全清楚。相比之下，肠道共生细菌已被证明通过与宿主的先天性和适应性免疫系统相互作用而对肠道保护机制做出贡献。口腔和肠道环境相似，因为它们都携带着沉重的微生物负担，而且都位于宿主组织旁边，这些组织需要保持无菌状态才能充分发挥作用和健康。具体地说，牙周组织是高度血管化的，提供了一种细菌或其成分可以进入血液并可能导致系统性疾病的手段。因此，研究表明，人类和啮齿动物的牙周组织中都含有不寻常的持续大量中性粒细胞从高度血管化的牙周组织流向牙周缝隙，在那里它们是主要的宿主保护机制。然而，人们对牙周组织如何协调这种持续的炎症监测机制知之甚少。在这项建议中，我们的总体假设是“口腔共生细菌通过选择性表达中性粒细胞趋化因子受体CXCR2配体来促进先天防御动态平衡。”这一假设将通过定义无菌和常规饲养小鼠的趋化因子配体表达的研究(特定目标1)，确定选定口腔细菌对趋化因子配体表达的贡献(特定目标2)，以及使用选定的基因敲除小鼠阐明宿主激活机制(特定目标3)来验证。这些研究将为理解这一关键的牙周宿主保护机制奠定基础，并可用于开发新的干预和预防治疗方法。

DESCRIPTION (provided by applicant): The contribution of oral commensal bacteria to oral health is not fully understood. In contrast, intestinal commensal bacteria have been shown to contribute to intestinal protection mechanisms though interactions with the host's innate and adaptive immune systems. The oral and intestinal environments are similar in that they both carry a heavy microbial burden and are located next to host tissues which need to remain sterile to be fully functioning and healthy. Specifically, the periodontium is highly vascularized providin a means by which bacteria or their components can enter the bloodstream and potentially contribute to systemic disease. Accordingly, studies have demonstrated that periodontal tissue in both humans and rodents contain an unusual constant heavy flow of neutrophils from the highly vascularized periodontal tissue to the gingival crevice where they serve as a major host protection mechanism. However, little is known how periodontal tissue orchestrates this constant inflammatory surveillance mechanism. In this proposal our overall hypothesis is that "oral commensal bacteria contribute to innate defense homeostasis by the selective expression of neutrophil chemokine receptor CXCR2 ligands." This hypothesis will be examined by studies defining chemokine ligand expression in germ free and conventionally reared mice (Specific Aim 1), determining the contribution of select oral bacteria to chemokine ligand expression (Specific aim 2), and elucidating host activation mechanisms with the use of select knockout mice (Specific aim 3). These studies will lay a foundation for understanding this key periodontal host protection mechanism which can then be used to develop novel intervention and preventative therapies.