Determinants of Intra-abdominal Abscess Formation

腹内脓肿形成的决定因素

• 批准号: 7999908
• 负责人: Neeraj K Surana
• 金额: $ 5.33万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7999908
• 关键词: Abdominal Abscess; Abdominal Infection; Abscess; Anaerobic Bacteria; Bacterial Infections; Bacteroides fragilis; Biological Response Modifiers; Disease; Extravasation; Immune response; Immune system; Infection; Interleukin-17; Lead; Molecular; Morbidity - disease rate; Nature; Organism; Pathologic; Patients; Polysaccharides; Production; Public Health; Research; Role; Source; T-Lymphocyte; Work; gastrointestinal system; immune function; insight; member; novel; novel therapeutics; prevent; public health relevance; research study; response

DESCRIPTION (provided by applicant): The gram-negative anaerobe Bacteroides fragilis is an integral member of the mammalian gastrointestinal system. It is also the most frequently isolated organism from intra-abdominal abscesses, which generally arise from spillage of colonic contents and result in severe morbidity for patients. Previous work has demonstrated that the zwitterionic nature of the capsular polysaccharides found on B. fragilis is essential for abscess formation and that IL-17 is a critical component of the host immune response. The experiments outlined in this application seek to better understand the molecular underpinnings of intra-abdominal abscess formation by further exploring its determinants as related to both the innate immune system and commensal flora. In the first aim, we will identify the cellular and bacterial determinants of IL-17 production in B. fragilis infection. In the second aim, we will explore the role of the microbiota in intra-abdominal abscess formation. We hypothesize that gd T cells are a critical, early source of IL-17 required for abscess formation and that this production is influenced by specific commensal organisms. Taken together, these experiments will provide insight into the relationship between the microbiota, host immune function, and disease. Moreover, the proposed studies may provide novel therapeutic paradigms to treat and/or prevent bacterial infections. PUBLIC HEALTH RELEVANCE: The experiments outlined in this application study the immune mediators of a classic pathologic response to infection - abscess formation. These studies will broaden our understanding of the interplay between commensal organisms, abdominal infections, and the host immune response and has the potential to lead to novel paradigms to treat and/or prevent bacterial infections.

描述(申请人提供)：革兰氏阴性厌氧菌脆弱类杆菌是哺乳动物胃肠道系统中不可或缺的一员。它也是最常见的从腹内脓肿中分离出来的微生物，通常由结肠内容物溢出引起，并导致患者严重的发病率。以前的工作已经证明，脆弱芽孢杆菌囊膜多糖的两性离子性质对于脓肿的形成是必不可少的，而IL-17是宿主免疫反应的关键成分。本申请中概述的实验旨在通过进一步探索与先天免疫系统和共生菌群相关的决定因素，更好地了解腹内脓肿形成的分子基础。在第一个目标中，我们将确定在脆弱芽孢杆菌感染中产生IL-17的细胞和细菌决定因素。在第二个目标中，我们将探索微生物区系在腹内脓肿形成中的作用。我们假设gdT细胞是脓肿形成所需的IL-17的关键的早期来源，并且这种产生受到特定共生生物的影响。综上所述，这些实验将深入了解微生物区系、宿主免疫功能和疾病之间的关系。此外，拟议的研究可能为治疗和/或预防细菌感染提供新的治疗范例。 公共卫生相关性：本申请中概述的实验研究感染-脓肿形成的经典病理反应的免疫介质。这些研究将扩大我们对共生生物、腹部感染和宿主免疫反应之间的相互作用的理解，并有可能导致治疗和/或预防细菌感染的新范例。