Host and Bacterial Factors in Disease due to H. Pylori

幽门螺杆菌疾病的宿主和细菌因素

• 批准号: 7730235
• 负责人: KATHRYN A. EATON
• 金额: $ 35.95万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7730235
• 关键词: Adoptive Transfer; Antibodies; Autopsy; C57BL/6 Mouse; CD4 Positive T Lymphocytes; Cell Culture Techniques; Cells; Clinical; Communicable Diseases; Data; Development; Disease; Employment; Ensure; Equilibrium; Flow Cytometry; Gastritis; Goals; Gray unit of radiation dose; Helicobacter Infections; Helicobacter pylori; Helper-Inducer T-Lymphocyte; Human; Immune; Immune response; Immune system; Immunochemistry; Individual; Infection; Inflammation; Integration Host Factors; Interferons; Interleukin-10; Interleukin-17; Laboratories; Laboratory Technicians; Lead; Malignant Neoplasms; Minority; Modeling; Mus; Outcome; Pathway interactions; Peptic Ulcer; Population; Publishing; Recovery; Regulation; Resistance; Role; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Time; congenic; cytokine; disorder risk; graduate student; research study; time interval; transcription factor

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.

幽门螺杆菌仍然是世界上最普遍的传染病，在某些人群中，高达100％的人被定居。然而，由于幽门螺杆菌引起的疾病是可变的：只有少数受感染的个体会发展出临床疾病。越来越清楚的是，这种变异性归因于宿主免疫反应的差异，并且了解导致疾病的免疫机制对于控制胃炎和随后的后遗症，例如消化性溃疡疾病和癌症至关重要。我们的实验室使用既定的收养转移模型来研究对幽门螺杆菌的适应性免疫反应。 CD4（助手）T细胞是必要的，足以诱导幽门螺杆菌感染小鼠的疾病，调节性T细胞抑制胃炎。感染与IFN_有关，但最近的数据表明，与以前的假设相反，包括Th1，Th17，可能还有其他可能导致幽门螺杆菌引起的胃炎。我们的中心假设是，TH-1，TH-17和T调节细胞之间的平衡决定了幽门螺杆菌引起的胃炎的结果。我们的总体目标是确定Th-1和Th-17之间交叉调节在调节胃炎中的作用，并确定Treg细胞在抑制Th-1独立和TH-17独立胃炎中的机制。两个具体目的是：目标1：确定幽门螺杆菌胃炎中IFN_和IL-17之间的相互作用。目标2：确定CD4CD25FOXP3+调节性T细胞通过幽门螺杆菌引起的Th1-或Th17独立炎症的机制。在此修订中，我们消除了长期实验，从而减少了要使用的小鼠数量。这将使我们能够雇用更多的员工，以确保快速完成其余实验。通过这些更改，我们完全期望在两年内完成这些实验。