GI Nematodes and Gut Functional Responses to Inflammation

一种免疫介导的结肠炎保护作用和改善的结肠 功能。我们的初步数据使我们在这项提案中将努力集中在以下具体机制上： 肠道感染会改变肠道功能。拟议的研究包含三个特定的目标，旨在测试 以下两个中心假设：1)感染诱导的肠道发育和变化的持续时间 功能是由细胞因子对结构细胞的直接作用和细胞间的相互作用所介导的。 结构和免疫细胞(特异性目标1和2)；和2)IL-17细胞因子家族的成员 在调节与Th1或Th2谱相关的功能效应方面很重要(具体目标3)。这个 建议的方法将使用感染天然啮齿动物病原体的小鼠，在体内和体外进行研究 粘膜和平滑肌功能，免疫细胞的原代培养，以及分子和 免疫组织化学分析。这些研究将帮助我们了解寄主是如何利用生理 它对病原体的防御机制允许促进促进 开除。这些研究的影响很明显地体现在这些功能变化的失调上 显著损害寄主抵抗力，维持足够的屏障功能和养分吸收。 这些研究还将提供有关线虫感染能力的机制的洞察 防止自身免疫性疾病的发展，其中许多疾病的特点是受损 肠道屏障功能。 项目说明第6页

an immune-mediated protection against colitis along with improved colonic function. Our preliminary data led us to focus our efforts in this proposal on the specific mechanisms by which enteric infection alters gut function. The proposed studies contain 3 specific aims that are designed to test the following two central hypotheses: 1) infection-induced development and duration of changes in gut function are mediated by direct effects of cytokines on structural cells and on the interaction between structural and immune cells (Specific Aims 1 and 2); and 2) members of the IL-17 cytokine family are important in regulation of the functional effects associated with the Th1 or Th2 profiles (Specific Aim 3). The proposed approach will use mice infected with natural rodent pathogens, in vivo and in vitro studies of mucosal and smooth muscle function, primary cultures of immune cells, and molecular and immunohistochemical analyses. These studies will help us to understand how the host exploits physiological mechanisms in its defense against pathogens that allow for the stereotypic functional responses that promote expulsion. The impact of these studies is evident in that dysregulation of these functional changes significantly impairs host resistance and the maintenance of adequate barrier function and nutrient absorption. These studies also will provide insight on the mechanisms involved in the ability of nematode infection to protect against the development of autoimmune diseases, many of which are characterized by impaired intestinal barrier function. Project Description Page 6