CYSTEINE PROTEINASES AS LEISHMANIAL VIRULENCE FACTORS

半胱氨酸蛋白酶作为利什曼原虫毒力因子

• 批准号: 6372709
• 负责人: LAURENCE U BUXBAUM
• 金额: $ 12.58万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6372709
• 关键词: Leishmania major; cellular immunity; cysteine endopeptidases; host organism interaction; laboratory mouse; microorganism genetics; protease inhibitor; virulence; wound healing

DESCRIPTION (adapted from application abstract): This application is based on the finding that C3H mice develop chronic non-healing lesions when infected with L. mexicana, but mount a strong healing Th1 response to infections caused by L. mexicana lacking the cysteine proteinase b genes (cpb organisms). By characterizing differences in host immune responses to these parasites, it is possible to eliminate confounding genetic variables in host and parasite species. The underlying hypothesis is that cysteine proteinases are involved in suppressing the cell-mediated responses needed for disease cure without engendering a Th2-type response. This is in contrast to the susceptibility of BALB/c mice to L. major, which is Th2-driven. The PI proposes to test the ability of exogenous cysteine proteinases to suppress a healing immune response to L. mexicana and L. major. The project has the potential to help demonstrate that cysteine proteinases are useful targets for vaccine and drug therapies. He will also define the role of cysteine proteinases as virulence factors using inhibitors and transfection methodologies. The candidate has an M.D. and Ph.D. degrees, with thesis research in the GPI anchor of African trypanosomes. He has completed his clinical training in Internal Medicine and a clinical year of Infectious Diseases at the University of Pennsylvania.

描述（改编自应用摘要）：本应用基于 C3 H小鼠感染后会出现慢性不愈合病变， 与L.墨西哥，但安装一个强大的愈合Th 1反应感染引起的 由L.缺少半胱氨酸蛋白酶B基因（cpB生物）的墨西哥亚种。 通过 表征宿主对这些寄生虫的免疫反应的差异， 可能消除宿主和寄生虫中的混淆遗传变量 物种 潜在的假设是，半胱氨酸蛋白酶参与 抑制疾病治疗所需的细胞介导的反应， 产生Th 2型应答。 这是与敏感性的对比。 BALB/c小鼠接种L.主要是Th 2驱动的。 PI建议测试 外源性半胱氨酸蛋白酶抑制愈合免疫的能力 回应L。mexicana和L.少校 该项目有可能帮助 证明半胱氨酸蛋白酶是疫苗和药物的有用靶标 治疗 他还将半胱氨酸蛋白酶的作用定义为毒力 因子使用抑制剂和转染方法。候选人有一个 M.D.和博士学位，论文研究在非洲的GPI锚 锥虫 他完成了内科临床培训， 宾夕法尼亚大学传染病临床年