Commensal Bacteria in Regulation Of T gondii Induced IBD

提出的研究探讨弓形虫和共生菌群在病原体驱动的炎症性肠病（IBD）实验模型的免疫调节中的相互作用。需要验证的假设是，来自共生肠道菌群的特定细菌产物可以与寄生虫感染的宿主相互作用，并防止实验性IBD的发展。我们观察到，无菌小鼠在口腔寄生虫感染后比常规小鼠更容易出现回肠和结肠的急性坏死性疾病，这表明肠道菌群或其衍生产物是预防弓形虫诱导的IBD发展所必需的。在第一个具体目标中，我们将比较肠道组织样本（表型，趋化因子细胞因子的产生）

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.