Host and Bacterial Factors in Disease due to H. Pylori

幽门螺杆菌仍然是世界上最流行的传染病，在某些人群中高达100%的人定植。疾病由于H。然而，幽门螺杆菌是可变的：只有少数感染个体发展为临床疾病。越来越清楚的是，这种变异性可归因于宿主免疫反应的差异，并且理解有助于疾病的免疫机制对于控制胃炎和随后的后遗症如消化性溃疡疾病和癌症将是至关重要的。本实验室利用已建立的过继转移模型研究了H.幽门。CD 4（辅助）T细胞是诱导H. pylori感染的小鼠，调节性T细胞抑制胃炎。感染与IFN-γ有关，但最近的数据表明，与以前的假设相反，包括Th 1，Th 17在内的几种免疫途径以及可能的其他途径导致H.幽门。我们的中心假设是Th-1、Th-17和调节性T细胞之间的平衡决定了H.幽门。我们的总体目标是确定Th-1和Th-17之间的交叉调节在胃炎调节中的作用，并确定Treg细胞抑制Th-1非依赖性胃炎和Th-17非依赖性胃炎的机制。目的1：研究IFN-γ与IL-17在H.幽门胃炎目的2：探讨CD 4CD 25 Foxp 3+调节性T细胞对H.幽门。在这次修订中，我们取消了长期实验，从而减少了使用的小鼠数量。这将使我们能够雇用更多的工作人员，以确保迅速完成剩余的实验。通过这些变化，我们完全期望在两年内完成这些实验。

Helicobacter pylori remains the most prevalent infectious disease in the world, with up to100% of people colonized in some populations. Disease due to H. pylori is variable, however: only a minority of infected individuals develops clinical disease. It has become increasingly clear that this variability is attributable to differences in host immune response, and that understanding the immune mechanisms that contribute to disease will be essential for controlling gastritis and the subsequent sequelae such as peptic ulcer disease and cancer. Our laboratory uses an established adoptive transfer model to study the adaptive immune response to H. pylori. CD4 (helper) T cells are necessary and sufficient to induce disease in H. pylori infected mice, and regulatory T cells suppress gastritis. Infection is associated with IFN_ but recent data indicate that, contrary to previous assumptions, several immune pathways including Th1, Th17, and possibly others contribute to gastritis due to H. pylori. Our central hypothesis is that the balance between Th-1, Th-17, and T regulatory cells determines the outcome of gastritis due to H. pylori. Our overall goals are to determine the role of cross-regulation between Th-1 and Th-17 in regulation of gastritis and to determine the mechanism of Treg cells in suppression of Th-1 independent and Th-17 independent gastritis. The two specific aims are: Aim 1: To determine the interactions between IFN_ and IL-17 in H. pylori gastritis. Aim 2: To determine the mechanism by which CD4CD25Foxp3+ regulatory T cells regulate Th1- or Th17- independent inflammation due to H. pylori. In this revision we have eliminated long-term experiments and thereby decreased the number of mice to be used. This will allow us to hire additional staff to ensure rapid completion of the remaining experiments. With these changes we fully expect to complete these experiments in 2 years.