Filifactor alocis interactions with neutrophils

Filifactor alocis 与中性粒细胞的相互作用

• 批准号: 8747218
• 负责人: Silvia M Uriarte
• 金额: $ 36.65万
• 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/8747218
• 关键词: Adult; Affect; Animal Model; Bacteria; Bacterial Infections; Biology; Cells; Chronic; Communicable Diseases; Cytoplasmic Granules; Data; Development; Diagnostic; Disease; Disorder by Site; 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; neutrophil; novel therapeutic intervention; novel therapeutics; oral bacteria; oral pathogen; pathogen; pathogenic bacteria; public health relevance; response; retinal rods; subcutaneous; trafficking

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.

摘要 牙周炎是一种由微生物引起的慢性炎症性疾病， 牙齿。随着高通量测序技术的发展及其在口腔癌基因组中的应用， 微生物，一些新认识的生物体已被认为与牙周炎有关。 病变其中包括革兰氏阳性厌氧杆菌Filifactoralocis， 牙周病部位与健康部位比较。然而，关联并不能建立因果关系， 目前的挑战是确定F. alocis。慢性炎症性传染病 牙周炎等疾病的发生是因为病原体能够逃避或使先天性牙周炎丧失功能， 免疫系统中性粒细胞是先天性宿主应答的主要成分，并且是免疫应答的结果。 牙周病原体和嗜中性粒细胞之间的相互作用是口腔健康状况的关键决定因素。一个 因此，了解微生物和宿主因素对于增加我们对 牙周病的治疗方法目前的建议将测试的假设，Filifactoralocis调节 中性粒细胞功能反应作为免疫逃避策略，以避免杀伤和促进炎症。我们 我们将通过以下具体目标来检验我们的假设：目标1：描述中性粒细胞呼吸爆发 回答F。alocis挑战。这个目标的目标将是测试的假设，F。失活刺激 导致选择性中性粒细胞反应的功能障碍，从而损害细菌杀伤。目标2： 表征中性粒细胞对F. alocis挑战。这个目标 目的是检验F. alocis将调节中性粒细胞脱粒，从而破坏 中性粒细胞抗菌机制。目的3：研究F. alocis对中性粒细胞募集的影响， 在动物模型中激活。这个目标的目标将是测试的假设，F。alocis感染将 刺激中性粒细胞募集、活化和基质金属蛋白酶释放以促进炎症， vivo.目前的项目是一个新的/早期阶段的研究人员的合作努力， 中性粒细胞生物学和炎症（Uriarte博士）和口腔病原体和宿主细胞领域的专家 回复（拉蒙博士）。拟议的合作努力提供了一个创新和强大的框架，以研究 F.嗜中性粒细胞。此外，从该应用程序生成的数据是 开发新型治疗药物所需信息的必要组成部分 牙周病的治疗方法