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.
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.
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