Filifactor alocis interactions with neutrophils

摘要 牙周炎是一种由微生物引起的慢性炎症性疾病，影响牙龈组织的支持 牙齿。随着高通量测序技术的发展，以及它们在口腔中的应用 微生物区系，几种新认识的微生物已被认为与牙周有关 损伤。其中包括革兰氏阳性厌氧菌Filifactoralocis，该菌在 牙周疾病部位与健康部位的比较。然而，关联并不建立因果关系，而且 现在的挑战是确定弗洛克斯氏杆菌的潜在致病性。慢性炎症性感染 牙周炎等疾病的发生是因为病原体能够躲避或使先天的 免疫系统。中性粒细胞是先天宿主反应的主要组成部分，其结果是 牙周病原体和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，对微生物和寄主因素的了解对于增加我们对 牙周病过程。目前的提议将检验Filifactoralocis调节 中性粒细胞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验证我们的假设：目标1：表征中性粒细胞呼吸爆发 对F.alocis挑战的回应。这个目标的目的将是检验这样一种假设，即阿洛克斯氏菌的刺激 导致选定的中性粒细胞反应功能障碍，从而影响细菌杀灭。目标2：实现 描述中性粒细胞氧非依赖性抗菌素对金黄色葡萄球菌挑战的反应。这样做的目的是 目的是验证这样的假设，即金黄色葡萄球菌将调节中性粒细胞脱颗粒，从而颠覆 中性粒细胞抗菌机制。目的3：研究金针菇对中性粒细胞募集的影响，并探讨其作用机制。 在动物模型中激活。这一目标的目的将是检验这样一种假设，即阿洛克斯菌感染将 刺激中性粒细胞募集、激活和基质金属蛋白酶释放以促进炎症反应 活着。目前的项目是一个新的/早期阶段的调查员的合作努力，具有以下方面的专业知识 中性粒细胞生物学和炎症(乌里亚特博士)，口腔病原体和宿主细胞领域的专家 回答(拉蒙特博士)。拟议的合作努力为研究提供了一个创新和强有力的框架 金黄色葡萄球菌与中性粒细胞的相互作用。此外，此应用程序生成的数据是 允许开发新型治疗方法所需的信息的必要组成部分 控制牙周病的策略。

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.