Filifactor alocis interactions with neutrophils

描述（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，影响支持牙齿的牙龈组织。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，一些新发现的生物体已被认为与牙周病变相关。其中包括革兰氏阳性厌氧杆菌Filifactoralocis，与健康部位相比，它在牙周病部位中的数量很高。然而，关联并不能建立因果关系，现在的挑战是确定F。alocis。慢性炎症性感染性疾病如牙周炎的发生是因为病原体能够逃避或使先天免疫系统失效。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。目前的建议将测试的假设，Filifactoralocis调节中性粒细胞的功能反应作为一种免疫逃避策略，以避免杀死和促进炎症。我们将通过以下具体目标来检验我们的假设：目的1：描述中性粒细胞对F的呼吸爆发反应。alocis挑战。这个目标的目标将是测试的假设，F。Alocis刺激引起选择的嗜中性粒细胞应答的功能障碍，从而损害细菌杀伤。目的2：研究中性粒细胞对F. alocis挑战。这个目标的目标将是测试的假设，F。Alocis将调节嗜中性粒细胞脱粒，从而破坏嗜中性粒细胞抗微生物机制。目的3：研究F. alocis在动物模型中对中性粒细胞募集和活化的影响。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，从而促进体内炎症。目前的项目是一个新的/早期阶段的研究者在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反应领域的专家（拉蒙博士）的专业知识的合作努力。拟议的合作努力为研究F之间的相互作用提供了一个创新且强大的框架。嗜中性粒细胞。此外，从该应用程序中生成的数据是必要的信息组成部分，这些信息将被要求允许开发用于控制牙周病的新治疗策略。

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.