MURINE MODELS OF PNEUMOCYSTIS CARINII INFECTION

卡氏肺囊虫感染的小鼠模型

• 批准号: 3139341
• 负责人: CHARLES L SIDMAN
• 金额: $ 17.76万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-15 至 1992-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3139341
• 关键词: AIDS; HIV infections; Pneumocystis; Pneumocystis pneumonia; T lymphocyte; cytokine; disease /disorder model; gene mutation; genetic library; genetic manipulation; genetic strain; host organism interaction; human immunodeficiency virus 1; immunocytochemistry; immunotherapy; in situ hybridization; laboratory mouse; microorganism genetics; microorganism immunology; microorganism interaction; model design /development; molecular cloning; monoclonal antibody; opportunistic infections; protozoal antigen

Infection by optic pathogens such as Pneumocystis carinii (Pc) constitute the major fatal consequence of Human Immunodeficiency Virus HIV-induced Acquired Immunodeficiency Syndrome (AIDS). Since the number of disposed AIDS patients continues to increase worldwide, these opportunistic infections represent major and increasing public health challenges. The basic biology and genetics of the host-opportunistic pathogen interaction are not yet well understood, however. Moreover, restoration of immune function to an immunocompromised individual presents opportunities for either successful resolution of opportunistic infections or for inflammatory reactions themselves fatal to the host. With new drugs being developed to hold HIV and opportunistic infections temporarily at bay, and with hope of an eventual cure of HIV through molecular genetics, increasing numbers of patients will be faced with the challenge of reestablishing complete immune function and returning to normal life. This project will continue to utilize several genetically-defined mouse models to pursue the etiology, genetics, and therapy of Pc, via investigation of the following specific questions: 1) What are the effector mechanisms in pathogenesis from and immunity to Pc, and how can we provide protective or curative immunity with a minimum of harmful consequences? Previously developed cellular and humoral immunological reagents will be used to address these issues. 2) Which other microbial agents pathologically synergize with Pc, what are the mechanisms for such synergy, and how can we utilize the answers to these questions to choose the best targets and routes for therapy in cases of multiple infections? 3) What am the molecular and genetic determinants of Pc infectivity? Previously generated antibody and T cell reagents will be used to clone the gene and investigate the biology of the major antigenic protein of Pc, and to investigate the possible occurrence and relevance of Pc substrains. Standard genetic crosses will be used to reveal the genetic variables affecting host susceptibility to Pc.

光学病原体（例如肺炎史蒂斯氏菌（PC））的感染构成 人免疫缺陷病毒HIV诱导的主要致命后果 获得的免疫缺陷综合征（AIDS）。由于处置数量 艾滋病患者在全球范围内继续增加，这些机会主义 感染代表了主要的公共卫生挑战。这 宿主 - 运动病原体相互作用的基本生物学和遗传学 但是，尚不清楚。而且，免疫的恢复 对免疫功能低下的个人发挥作用 成功解决了机会性感染或 炎症反应本身对宿主致命。新药是 开发旨在将艾滋病毒和机会性感染暂时寄托，并 希望通过分子遗传学最终治愈艾滋病毒，增加 将面临重建的挑战的患者人数 完整的免疫功能并恢复正常生活。这个项目将 继续利用几种遗传定义的鼠标模型来追求 PC的病因，遗传学和疗法，通过研究以下 具体问题： 1）从和免疫到发病机理的效应机制是什么 PC，我们如何以最低限度提供保护性或治愈性免疫 有害后果？先前发展的细胞和体液 免疫试剂将用于解决这些问题。 2）其他微生物剂在病理上与PC协同作用，什么是 这种协同作用的机制，以及我们如何利用答案 这些问题可以在情况下选择最佳目标和治疗路线 多种感染？ 3）PC感染性的分子和遗传决定因素是什么？ 以前生成的抗体和T细胞试剂将用于克隆 基因并研究了PC的主要抗原蛋白的生物学， 研究PC底座的可能发生和相关性。 标准遗传杂交将用于揭示遗传变量 影响宿主对PC的敏感性。