Commensal Bacteria in Regulation Of T gondii Induced IBD

本研究旨在探讨弓形虫和肠道细菌植物群在病原体驱动的炎症性肠病（IBD）实验模型免疫调节中的相互作用。待检验的假设是，源自肠道植物群的特定细菌产物可与寄生虫感染的宿主相互作用并防止实验性IBD的发展。我们已经观察到，无菌小鼠比常规小鼠在经口寄生虫感染后更容易发生回肠和结肠的急性坏死状况，这表明需要肠道微生物菌群或其衍生产物来预防弓形虫诱导的IBD的发展。在第一个具体的目标，我们将比较肠道组织样本（表型，趋化因子细胞因子的生产）， 经口弓形虫感染常规小鼠后，抗性（BALB/c）和敏感（C57 BL/6）小鼠的无菌品系。我们已经确定了B的一个特定的荚膜多糖。fragilis可以调节肠道炎症过程。用来自脆弱拟杆菌的荚膜多糖（PSA）治疗常规小鼠可防止T。弓形虫感染IBD。粘膜组织，更具体地说，来自固有层、派伊尔集合淋巴结和其他淋巴结的淋巴细胞， 将评估来自PSA处理的常规和无菌小鼠的器官的免疫组织学差异。将进一步研究由PSA诱导的免疫调节的机制（IL-10、TGF-β产生）。正如我们的初步数据所表明的，特别关注的是产生TGF-β的CD 8+上皮内淋巴细胞（IEL）和IL-10依赖性CD 4调节性T细胞（CD 45 RB低，CD 25）。我们将评估这些调节性CD 4 + T细胞在PSA处理的小鼠的固有层和派伊尔集合淋巴结中的表达，并确定该细胞群是否可以适应性地转移到幼稚小鼠并预防弓形虫驱动的IBD。NKT细胞也是响应多糖的重要调节细胞。我们将评估PSA处理是否可以诱导发挥效应子和免疫调节活性的NKT细胞群体。

The proposed studies investigate the interaction of Toxoplasma gondii and commensal bacterial flora in the immune regulation of an experimental model of pathogen-driven inflammatory bowel disease (IBD). The hypothesis to be tested is that specific bacterial products derived from commensal intestinal flora can interact with the parasite-infected host and prevent the development of experimental IBD. We have observed that germ free mice are more susceptible to an acute necrotizing condition of the ileum and colon than conventional mice following oral parasite infection suggesting that intestinal microflora or their derived products are required to prevent the development of Toxoplasma induced IBD. In the first specific aim, we will compare intestinal tissue samples (phenotyping, chemokines cytokines production) in germ-free strains of resistant (BALB/c) and susceptible (C57BL/6) mice following oral Toxoplasma infection to conventional mice. We have identified a specific capsular polysaccharide of B. fragilis that can modulate the gut inflammatory process. Treatment of conventional mice with capsular polysaccharide (PS A) derived from Bacteroides fragilis prevents the development of T. gondii induced IBD. The mucosal tissue and more specifically lymphoid cells from the lamina propria, Peyer's patches and other organs from PS A treated conventional and germ free mice will be assessed for immunohistologic differences. Mechanisms (IL-10, TGF-b production) of immunomodulation induced by the PS A will be further investigated. As suggested by our preliminary data, particular attention will focus on TGF-b producing CD8+ intraepithelial lymphocytes (IEL) and on a population of IL-10 dependent CD4 regulatory T cells (CD45RB low, CD25). We will evaluate for the expression of these regulatory CD4+ T cells in the lamina propria and Peyer's patches of PS A treated mice and determine whether this cell population can be adaptively transferred to naive mice and prevent toxoplasma-driven IBD. NKT cells are also important regulatory cells that respond to polysaccharides. We will evaluate whether PS A treatment can induce a population of NKT cells that exert effector and immunoregulatory activity.