Determinants of Intra-abdominal Abscess Formation

描述（由申请人提供）：革兰氏阴性厌氧菌脆弱拟杆菌是哺乳动物胃肠道系统不可或缺的成员。它也是腹内脓肿中最常见的分离生物，腹内脓肿通常由结肠内容物溢出引起，并导致患者严重的发病率。先前的研究表明，在脆弱芽孢杆菌上发现的荚膜多糖的两性离子性质对脓肿的形成至关重要，IL-17是宿主免疫反应的关键组成部分。本应用程序中概述的实验旨在通过进一步探索其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，我们将确定易碎芽孢杆菌感染中IL-17产生的细胞和细菌决定因素。在第二个目标中，我们将探讨微生物群在腹内脓肿形成中的作用。我们假设gd T细胞是脓肿形成所需的IL-17的关键早期来源，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群、宿主免疫功能和疾病之间的关系。此外，所提出的研究可能为治疗和/或预防细菌感染提供新的治疗范例。

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.