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Microbial nucleic acid sensing in periodontitis

牙周炎中的微生物核酸传感

基本信息

批准号：
9094493
负责人：
Sinem Esra Sahingur
金额：
$ 38.12万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-20 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9094493
关键词：
Adverse effects Affect Agonist Alveolar Bone Loss Arterial Fatty Streak Arthritis Award Bacterial DNA Biological Biopsy Bone Marrow C5a anaphylatoxin receptor Cells Chronic Clinical Clinical Research Communication Complement Complement 5a DNA Dendritic Cells Disease Disease Outcome Distant Environment Future Gene Expression Genes Gingiva Greater sac of peritoneum Health Human Immunohistochemistry In Vitro Individual Infection Inflammation Inflammation Mediators Inflammatory Inflammatory Response Injection of therapeutic agent Investigation Knockout Mice Lead Lesion Ligands Ligature Link Mediating Microbe Modeling Molecular Mus Myeloid Cells Natural Immunity Nucleic Acids Oral Oral cavity Pathogenesis Pathway interactions Pattern Periodontal Diseases Periodontitis Physiological Population Porphyromonas gingivalis Production Receptor Activation Resistance Role Signal Transduction Signaling Molecule Site Source Synovial Fluid Systemic disease TLR2 gene TLR9 gene Testing Therapeutic Therapeutic Effect Time Tissues alveolar bone bone bone loss cytokine design in vivo inhibitor/antagonist macrophage microbial microbiome monocyte neutrophil novel prevent protein expression receptor response sensor therapeutic target translational approach

项目摘要

DESCRIPTION (provided by applicant): Microbial nucleic acids represent a group of microbe-associated molecular patterns that are recognized through intracellular innate sensors triggering inflammatory responses. Toll like receptor 9 (TLR9) is the major receptor for microbial DNA. Using a reverse translational approach, we revealed that TLR9 contributes to periodontal disease pathogenesis through exacerbating the local inflammatory responses. Current proposal will extend our previous studies to fully characterize the biological pathways and cellular sources of TLR9-triggered inflammation in periodontitis. We will determine both the non-redundant as well as cooperative role of TLR9 with other innate sensors implicated in periodontitis. The effect of TLR9 inhibitors to periodontal disease outcome will also be evaluated. Periodontal disease is not only limited to gingival tissues but also is associated with various systemic diseases. Identification of periodontal microbial DNA at distant sites suggests that microbial nucleic acid sensing may not be only important in periodontal disease pathogenesis but also contributes to periodontal disease adverse effects on systemic health. Therefore, the proposed studies will not only identify novel biological pathways and therapeutic targets to control local persistent periodontal inflammation but also lead to future investigations to identify a novel link between periodontitis and systemic complications.

描述（由申请人提供）：微生物核酸代表一组微生物相关分子模式，其通过细胞内先天传感器识别，触发炎症反应。Toll样受体9（TLR9）是微生物DNA的主要受体。使用反向翻译的方法，我们发现TLR9有助于牙周病的发病机制，通过加剧局部炎症反应。目前的建议将扩展我们以前的研究，以充分表征牙周炎中TLR9引发炎症的生物学途径和细胞来源。我们将确定TLR9与牙周炎中涉及的其他先天传感器的非冗余以及合作作用。还将评估TLR9抑制剂对牙周病结果的影响。牙周病不仅限于牙龈组织，而且还与各种全身性疾病有关。牙周微生物DNA在遥远的网站的鉴定表明，微生物核酸传感可能不仅是重要的牙周病的发病机制，但也有助于牙周病对全身健康的不良影响。因此，这些研究不仅将确定新的生物学途径和治疗靶点，以控制局部持续性牙周炎症，而且还将导致未来的研究以确定牙周炎和全身并发症之间的新联系。