Filifactor alocis interactions with neutrophils

Filifactor alocis 与中性粒细胞的相互作用

• 批准号: 9024353
• 负责人: Silvia M Uriarte
• 金额: $ 37.34万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9024353
• 关键词: Adult; Affect; Animal Model; Bacteria; Bacterial Infections; Biology; Cells; Chronic; Communicable Diseases; Cytoplasmic Granules; Data; Development; Diagnostic; Disease; Enzymes; Etiology; Exocytosis; Functional disorder; Future; Gingiva; Goals; Health; Health Status; High-Throughput Nucleotide Sequencing; Human; Immune; Immune response; Immune system; In Vitro; Infection; Inflammation; Inflammatory; Integration Host Factors; Intention; Knockout Mice; Knowledge; Lesion; Leukocytes; Maintenance; Matrix Metalloproteinases; Modeling; Mus; Neutrophil Activation; Neutrophil Infiltration; Oral; Oral health; Organism; Outcome; Oxygen; Particulate; Pathogenesis; Pathogenicity; Periodontal Diseases; Periodontitis; Phagosomes; Population; Porphyromonas gingivalis; Process; Research; Research Personnel; Respiratory Burst; Role; Site; Staging; Stimulus; TLR2 gene; Technology; Testing; Tissues; Tooth structure; United States; abstracting; antimicrobial; combat; in vivo; innovation; killings; microbial; microbial host; microbiota; neutrophil; novel therapeutic intervention; novel therapeutics; oral bacteria; oral pathogen; pathogen; pathogenic bacteria; response; retinal rods; subcutaneous; trafficking

DESCRIPTION (provided by applicant): Abstract Periodontitis is a microbial-induced chronic inflammatory disease that affects the gingival tissues supporting the tooth. With the development of high-throughput sequencing technologies, and their application to the oral microbiota, several newly appreciated organisms have become recognized as associated with periodontal lesions. Among these is the Gram-positive anaerobic rod Filifactor alocis which is present in high numbers in periodontal disease sites compared to healthy sites. However, association does not establish causality, and the challenge now is to determine the potential pathogenicity of F. alocis. Chronic inflammatory infectious diseases such as periodontitis can occur because the pathogens are able to evade or disable the innate immune system. Neutrophils are a major component of the innate host response and the outcome of the interaction between periodontal pathogens and neutrophils is a key determinant of oral health status. An understanding of both microbial and host factors is therefore essential to increase our knowledge of the periodontal disease process. The current proposal will test the hypothesis that Filifactor alocis modulates neutrophil functional responses as an immune evasion strategy to avoid killing and promote inflammation. We will test our hypothesis by the following specific aims: Aim 1: To characterize neutrophil respiratory burst response to F. alocis challenge. The goal of this aim will be to test the hypothesis that F. alocis stimulation causes dysfunction of select neutrophil responses, and thus compromises bacterial killing. Aim 2: To characterize the neutrophil oxygen-independent antimicrobial response to F. alocis challenge. The goal of this aim will be to test the hypothesis that F. alocis will modulate neutrophil degranulation and thus subvert neutrophil antimicrobial mechanisms. Aim 3: To determine the effect of F. alocis on neutrophil recruitment and activation in an animal model. The goal of this aim will be to test the hypothesis that F. alocis infection will stimulate neutrophil recruitment, activation, and matrix metalloproteinases release to promote inflammation in vivo. The current project is a collaborative effort from a new/early stage investigator with expertise in neutrophil biology and inflammation (Dr. Uriarte) and an expert in the field of oral pathogens and host cell responses (Dr. Lamont). The proposed collaborative efforts offer an innovative and strong framework to study the interaction between F. alocis and neutrophils. Furthermore, the data generated from this application are a necessary component of the information that will be required to allow the development of novel therapeutic strategies for controlling periodontal disease.

描述（由申请人提供）： 摘要牙周炎是一种微生物引起的慢性炎症性疾病，影响支撑牙齿的牙龈组织。随着高通量测序技术的发展及其在口腔微生物群中的应用，一些新近被认识的微生物已被认为与牙周病变有关。其中包括革兰氏阳性厌氧菌 Filifactor alocis，与健康部位相比，它在牙周病部位的数量较多。然而，关联并不能确定因果关系，现在的挑战是确定 F. alocis 的潜在致病性。由于病原体能够逃避或禁用先天免疫系统，因此可能会发生牙周炎等慢性炎症传染病。中性粒细胞是先天宿主反应的主要组成部分，牙周病原体和中性粒细胞之间相互作用的结果是口腔健康状况的关键决定因素。因此，了解微生物和宿主因素对于增加我们对牙周病过程的了解至关重要。目前的提案将检验以下假设：Filifactor alocis 调节中性粒细胞功能反应，作为避免杀伤和促进炎症的免疫逃避策略。我们将通过以下具体目标来检验我们的假设： 目标 1：表征中性粒细胞对 F. alocis 攻击的呼吸爆发反应。该目的的目的是检验以下假设：F. alocis 刺激会导致特定中性粒细胞反应功能障碍，从而损害细菌杀灭。目标 2：表征中性粒细胞对 F. alocis 攻击的不依赖氧的抗菌反应。该目的的目的是检验 F. alocis 将调节中性粒细胞脱颗粒并从而颠覆中性粒细胞抗菌机制的假设。目标 3：确定 F. alocis 对动物模型中中性粒细胞募集和激活的影响。该目的的目的是检验以下假设：F. alocis 感染会刺激中性粒细胞募集、激活和基质金属蛋白酶释放，从而促进体内炎症。当前的项目是一位具有中性粒细胞生物学和炎症专业知识的新/早期研究人员（Uriarte 博士）和口腔病原体和宿主细胞反应领域的专家（Lamont 博士）的合作成果。拟议的合作努力为研究 F. alocis 和中性粒细胞之间的相互作用提供了一个创新且强大的框架。此外，从该应用程序生成的数据是开发控制牙周病的新治疗策略所需的信息的必要组成部分。