IMMUNOPATHOGENESIS OF CRYPTOSPORIDIOSIS

隐孢子虫病的免疫发病机制

• 批准号: 6170767
• 负责人: ROSEMARY SOAVE
• 金额: $ 8.73万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6170767
• 关键词: AIDS; Cryptosporidium; T lymphocyte; clinical research; cryptosporidiosis; gastrointestinal epithelium; host organism interaction; human subject; immunopathology; laboratory mouse; leukocyte activation /transformation; molecular cloning; monoclonal antibody; mucosal immunity; opportunistic infections; protein localization; protozoal antigen; tissue /cell culture

Both T- and B-cell mediated immunity are believed to play a role in the eradication of and protection from cryptosporidial infections but the mechanisms by which specific components of human host defense mediate successful immunity are unknown. Although many cryptosporidial proteins have been identified, neither their function nor their significance is known. The interaction of Cryptosporidium with its target host cell, the intestinal epithelial cell, and the role of parasite proteins in this interaction has also been little studied. In the proposed studies we will bring the experience and biological samples obtained in over ten years of clinical trials work to the bench in order to begin to unravel the mechanisms by which Cryptosporidium triggers an immune response by virtue of its interaction with the intestinal epithealial cell. In our preliminary analysis of serial serum samples from AIDS patients with chronic cryptosporidiosis, we found that complete clinical and parasitologic resolution of infection coincides with a brisk humoral immune response, and specifically with generation of immunoglobulin directed against a 33 kD cryptosporidial protein (p-33). This project focuses on characterization of p-33 and investigation of its potential role as a virulence factor. Furthermore, the proposed studies provide a novel approach to the study of immune function in cryptosporidial infection because they will focus on the potential role of p-33 as a T-cell antigen. Our specific aims are to: (1) characterize the 33 kD cryptosporidial protein, and (2) explore the potential role of p- 33 as a T-cell dependent antigen. As there are no models in place for work related to Aim 2, we have adopted an innovative approach for developing useful models for the study of intestinal immunity against Cryptosporidium.

T细胞和B细胞介导的免疫被认为在根除和保护隐孢子虫感染方面发挥着作用，但人类宿主防御的特定成分介导成功免疫的机制尚不清楚。尽管许多隐孢子虫蛋白已被鉴定，但它们的功能和意义尚不清楚。 隐孢子虫与其靶宿主细胞（肠上皮细胞）的相互作用以及寄生虫蛋白在这种相互作用中的作用也很少被研究。在拟议的研究中，我们将把十多年临床试验工作中获得的经验和生物样本带到工作台上，以便开始揭示隐孢子虫通过与肠上皮细胞相互作用触发免疫反应的机制。 在我们对患有慢性隐孢子虫病的 AIDS 患者的系列血清样本进行初步分析时，我们发现感染的临床和寄生虫学完全消退与快速的体液免疫反应相一致，特别是与针对 33 kD 隐孢子虫蛋白 (p-33) 的免疫球蛋白的产生相一致。该项目的重点是 p-33 的表征并研究其作为毒力因子的潜在作用。此外，拟议的研究为研究隐孢子虫感染中的免疫功能提供了一种新方法，因为它们将重点关注 p-33 作为 T 细胞抗原的潜在作用。我们的具体目标是：(1) 表征 33 kD 隐孢子虫蛋白，(2) 探索 p-33 作为 T 细胞依赖性抗原的潜在作用。 由于与目标 2 相关的工作没有适当的模型，我们采用了一种创新方法来开发有用的模型来研究隐孢子虫的肠道免疫。