Contribution of oral bacteria to healthy homeostasis

口腔细菌对健康体内平衡的贡献

• 批准号: 9185971
• 负责人: Richard Peters Darveau
• 金额: $ 34.71万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-20 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9185971
• 关键词: Adaptive Immune System; Animal Model; Bacteria; Blood Circulation; Blood Vessels; Cell Differentiation process; Cell Separation; Chemotaxis; Complement; Confocal Microscopy; Connective Tissue; Data; Defect; Dental Plaque; Development; Environment; Epithelial; Epithelium; Foundations; Future; Germ-Free; Gingiva; Health; Homeostasis; Host Defense; Host Defense Mechanism; Human; IL8RB gene; Immunohistochemistry; In Situ; Individual; Inflammatory; Interleukin-8B Receptor; Intestines; Knockout Mice; Ligands; Location; Maintenance; Mediating; Mus; Oral; Oral cavity; Oral health; Pathway interactions; Periodontitis; Periodontium; Preventive Intervention; Preventive therapy; Process; Reporting; Rodent; Sterility; Symbiosis; System; Systemic disease; TLR2 gene; TLR4 gene; Techniques; Therapeutic Intervention; Tissues; Tooth structure; bone loss; chemokine; chemokine receptor; commensal microbes; germ free condition; insight; microbial; migration; neutrophil; novel; oral bacteria; oral commensal; pathogenic bacteria; periopathogen; public health relevance; response; selective expression; trafficking

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.

描述（申请人提供）：口腔共生菌对口腔健康的贡献尚未完全了解。相比之下，肠道共生菌已被证明通过与宿主的先天和适应性免疫系统相互作用来促进肠道保护机制。口腔和肠道环境是相似的，因为它们都携带着沉重的微生物负担，并且位于宿主组织旁边，宿主组织需要保持无菌才能充分发挥功能和健康。具体来说，牙周组织是高度血管化的，提供了一个途径，细菌或它们的成分可以进入血液，并可能导致全身性疾病。因此，研究表明，人类和啮齿类动物的牙周组织都含有一种不寻常的、持续大量的中性粒细胞，它们从高度血管化的牙周组织流向龈缝，在龈缝中充当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。在这个提议中，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稳态。”这一假设将通过研究确定趋化因子配体在无菌和常规饲养小鼠中的表达（Specific Aim 1），确定选择口腔细菌对趋化因子配体表达的贡献（Specific Aim 2），以及使用选择敲除小鼠阐明宿主激活机制（Specific Aim 3）来验证。这些研究将为了解这一关键的牙周宿主保护机制奠定基础，然后可用于开发新的干预和预防疗法。