ALVEOLAR MACROPHAGES IN FIV INFECTION

五种感染中的肺泡巨噬细胞

• 批准号: 2671454
• 负责人: Jerry W Ritchey
• 金额: $ 8.86万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2671454
• 关键词: Retroviridae disease; Toxoplasma gondii; alveolar macrophages; autocrine; cats; cytokine; disease /disorder model; feline immunodeficiency virus; human immunodeficiency virus; immunologic assay /test; interferon gamma; interleukin 12; leukocyte activation /transformation; opportunistic infections

DESCRIPTION: (Adapted from the application) Critical to a better understanding of the pathogenesis of HIV-associated lung disease is an animal lentivirus model that parallels HIV-associated immunodeficiency. Evidence suggests that the feline AIDS-causing lentivirus, Feline Immunodeficiency Virus (FIV) causes serious pulmonary immunodeficiency characterized by increased susceptibility to Toxoplasma gondii pneumonia. The proposed research will employ the use of FIV for examining the defects in alveolar macrophage (AM) function. The application describes experiments designed to test two hypotheses: first, that the constitutive level of activation of AM from HIV/FIV patients is a direct result of viral infection of the AM independent of lymphokine conditioning; secondly, that HIV/FIV infection inhibits an autocrine interferon (IFN)-gamma loop necessary to prime AM for IL-12 production. a. Career Development Plan: The plan consists of two phases. During the first Phase, Dr. Ritchey will complete his Ph.D. training. He entered the Ph.D. program in July of 1993, and has completed the didactic training as well as the preliminary examination. In phase two (years three and four), Dr. Ritchey will remain at North Carolina State University, in a postdoctoral position. b. Research Plan: Feline Immunodeficiency Virus (FIV) will be used to examine the defects in alveolar macrophage (AM) function. Experiments are planned to test two hypotheses: first, that the constitutive level of activation of AM from HIV/FIV patients is a direct result of viral infection of the AM independent of lymphokine conditioning; secondly, that HIV/FIV infection inhibits an autocrine IFN-gamma loop necessary to prime AM for IL-12 production. Studies during the first three years of this program will test these hypotheses by evaluating cytokine expression patterns of AM collected in a temporal fashion following in vivo FIV infection. The last year of this research will correlate the results of the in vitro studies with in vivo challenge of FIV-infected cats with T. gondii.

描述：（改编自应用程序）对于更好的发展至关重要 了解 HIV 相关肺部疾病的发病机制是 与艾滋病毒相关免疫缺陷相似的动物慢病毒模型。 有证据表明，引起猫艾滋病的慢病毒，Feline 免疫缺陷病毒（FIV）导致严重的肺部免疫缺陷 其特点是对弓形虫肺炎的易感性增加。 拟议的研究将使用 FIV 来检查缺陷 肺泡巨噬细胞 (AM) 功能。 该应用程序描述了实验 旨在检验两个假设：第一，本构水平 HIV/FIV 患者的 AM 激活是病毒感染的直接结果 AM 的独立于淋巴因子调节；其次，HIV/FIV 感染抑制自分泌干扰素 (IFN)-γ 环，这是 用于IL-12生产的prime AM。 一个。职业发展计划：该计划分为两个阶段。 期间 第一阶段，Ritchey 博士将完成他的博士学位。训练。 他进入了 博士计划于1993年7月完成，并已完成教学培训 以及初步检查。 在第二阶段（第三年和第四年）， 里奇博士将留在北卡罗来纳州立大学 博士后职位。 b.研究计划：猫免疫缺陷病毒（FIV）将用于 检查肺泡巨噬细胞 (AM) 功能的缺陷。 实验是 计划检验两个假设：第一，本构水平 HIV/FIV 患者的 AM 激活是病毒感染的直接结果 AM 的独立于淋巴因子调节；其次，HIV/FIV 感染抑制自分泌 IFN-γ 环，这是启动 AM 所必需的 IL-12 生产。 该计划前三年的学习将 通过评估 AM 的细胞因子表达模式来检验这些假设 体内 FIV 感染后以时间方式收集。 最后一个 这项研究的年份将与体外研究的结果相关联 用弓形虫对感染 FIV 的猫进行体内攻击。