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: 6166270
• 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/6166270
• 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(改编自应用程序摘要)：此应用程序基于 C3H小鼠感染后出现慢性不可愈合损害的研究 对墨西哥乳杆菌，但对引起的感染有很强的治愈Th1反应 缺乏半胱氨酸蛋白酶b基因的墨西哥乳杆菌(CPB生物体)。通过 在描述宿主对这些寄生虫免疫反应的差异时， 可能消除寄主和寄生虫中的混杂遗传变量 物种。潜在的假设是半胱氨酸蛋白酶参与其中。 在抑制疾病治愈所需的细胞介导的反应中 产生Th2型反应。与此形成鲜明对比的是 BALB/c小鼠转至大白鼠，这是Th2驱动的。私人投资公司建议测试 外源性半胱氨酸蛋白酶抑制愈合性免疫的能力 对墨西哥乳杆菌和主要乳杆菌的反应。这个项目有潜力提供帮助。 证明半胱氨酸蛋白酶是疫苗和药物的有效靶点 治疗。他还将半胱氨酸蛋白酶的作用定义为毒力 使用抑制剂和转染法的因子。候选人有一个 医学和博士学位，论文研究非洲的GPI主播 锥虫。他已经完成了他的内科临床培训和 宾夕法尼亚大学传染病临床年。