IMMUNOPATHOLOGY OF MYCOBACTERIUM INTRACELLULARE IN AIDS

艾滋病细胞内分枝杆菌的免疫病理学

• 批准号: 3132381
• 负责人: PATTISAPU R GANGADHARAM
• 金额: $ 12.52万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3132381
• 关键词: AIDS; Actinomycetales infection; Mycobacterium avium; Mycobacterium intracellulare; bactericidal immunity; biomarker; communicable disease transmission; cyclophosphamide; delayed hypersensitivity; disease /disorder model; genetic strain; homosexuals; host organism interaction; human immunodeficiency virus; immunomodulators; immunopathology; immunosuppressive; interferons; interleukin 2; intravenous drug abuse; laboratory mouse; lysosomes; macrophage; microorganism culture; mutant; natural killer cells; opportunistic infections; phagocytosis; plasmids; serotyping; tissue /cell culture; virulence

Acquired immune deficiency syndrome (AIDS) has emerged as the most serious disease discovered in recent times. AIDS patients, whose immunity is drastically reduced by infection by the human immune deficiency virus (HIV) get more serious diseases with rapid fatalistic consequences, by several opportunistic infections. Most serious among these infections are those caused by Mycobacterium aviuim complex (MAC), with which this research project is concerned. The principal invesigator (PI) established that the beige mouse (C57B1/bgJ/bgJ) to be the most susceptibel mouse strain among several strains studied, to MAC infections. Beige mice get advanced acute MAC disease, with associated mortality, following intravenous, aerogenic, intraperitoneal, oral and intrarectal challenges, with evidence of increased disease following mulitple challenges over single exposures. Of particular relevance to the lifestyle of homosexual men, the vast majority of AIDS patients, are the single and multiple challenges via the intrarectal route. The PI had also shown that beige mice are similar to AIDS patients in many immunopathological features. Using single and multiple, intravenous and intrarectal challenges with virulent MAC, containing drug resistance markers, of beige and the parent C57B1/6 mice, this investigation explores why only 3 serotypes 1,4 and 8, among the 31 serotypes occurring in the evnironment are causing MAC disease in AIDS patients. Likewise, these studies inquire why all the MAC strains isolated from AIDS patients possessed plasmids, while only 5% of the environmental strains do so. Developing on the known and established immunobiological features of beige mice, these investigations examine why this mouse strain is most susceptible to MAC challenges. Absence of natural killer (NK) cell activity in beige mice is given great consideration in these studies. Finally, this project envisages several immunomodulations of the beige mice using immunosuppressive and immunopotentiating agents, specifically directed against NK cell activity. It is hoped that many of these studies will give important leads on the immunopathology of MAC disease in AIDS and immunotherapy of AIDS patients against MAC disease.

获得的免疫缺陷综合征（AIDS）已成为 最近发现的最严重的疾病。 艾滋病患者， 人类感染的免疫力大大降低了 免疫缺陷病毒（HIV）患有更严重的疾病 几种机会性感染，快速致命的后果。 这些感染中最严重的是由 分枝杆菌aviuim综合体（Mac），这项研究 项目很关心。 建立的主要入侵者（PI） 米色鼠标（C57B1/BGJ/BGJ）是最感动的 所研究的几种菌株中的小鼠应变，即MAC感染。 米色小鼠患高级急性MAC病，有相关的 死亡率，静脉注射，充气，腹膜内，口腔 和直肠内挑战，有疾病增加的证据 遵循对单一暴露的挑战。 特别 与同性恋者的生活方式相关，绝大多数 艾滋病患者是通过 直肠途径。 PI还表明米色小鼠是 与许多免疫病理学特征中的艾滋病患者类似。 使用单个和多个静脉内和直肠内挑战 用含有耐药性标记的有毒MAC，米色 和父级C57B1/6小鼠，此调查探讨了为什么仅 3种血清型1,4和8，在发生在31种血清型中 Evnironment正在引起艾滋病患者的MAC疾病。 同样地， 这些研究询问了为什么所有从艾滋病中分离出的MAC菌株 患者拥有质粒，而只有5％的环境 菌株这样做。 在已知和建立的 米色小鼠的免疫生物学特征，这些研究 检查为什么这种小鼠菌株最容易受到MAC的影响 挑战。 米色缺乏天然杀手（NK）细胞活性 在这些研究中，对小鼠进行了很好的考虑。 最后，这个 项目设想米色小鼠的几种免疫调节 使用免疫抑制和免疫抑制剂， 专门针对NK细胞活性。 希望 这些研究中的许多将为有关 MAC疾病的免疫病理学和免疫疗法 帮助患者反对MAC疾病。

项目成果

Murine models for mycobacterioses.

分枝杆菌病小鼠模型。

• 发表时间: 1986
• 期刊: Seminars in respiratory infections
• 作者: Gangadharam,PR

Comparison of virulence of Mycobacterium avium complex (MAC) strains isolated from AIDS and non-AIDS patients.

从 AIDS 和非 AIDS 患者中分离的鸟分枝杆菌复合体 (MAC) 菌株的毒力比较。

• DOI: 10.1006/mpat.1994.1013
• 发表时间: 1994
• 期刊: Microbial pathogenesis
• 影响因子: 3.8
• 作者: Reddy,VM;Parikh,K;Luna-Herrera,J;Falkinham3rd,JO;Brown,S;Gangadharam,PR
• 通讯作者: Gangadharam,PR

Utility of beige mouse in leprosy research.

米色小鼠在麻风病研究中的用途。

• 发表时间: 1992
• 期刊: Indian journal of leprosy
• 作者: Gangadharam,PR;Dhople,AM
• 通讯作者: Dhople,AM

Association of plasmids and virulence of Mycobacterium avium complex.

质粒与鸟分枝杆菌复合体毒力的关联。

• DOI: 10.1164/ajrccm/137.1.212
• 发表时间: 1988
• 期刊: The American review of respiratory disease
• 作者: Gangadharam,PR;Perumal,VK;Crawford,JT;Bates,JH
• 通讯作者: Bates,JH

An improved method for in vitro cultivation of murine splenic macrophages.

一种改进的小鼠脾巨噬细胞体外培养方法。

• DOI: 10.1007/bf02624420
• 发表时间: 1990
• 期刊: In vitro cellular & developmental biology : journal of the Tissue Culture Association
• 作者: Reddy,MV;Gangadharam,PR
• 通讯作者: Gangadharam,PR