PATHOGENESIS OF INTESTINAL CRYPTOSPORIDIOSIS IN AIDS

艾滋病肠道隐孢子虫病的发病机制

• 批准号: 3241052
• 负责人: Gerald T. Keusch
• 金额: $ 12.97万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-15 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3241052
• 关键词: AIDS; AIDS /HIV diagnosis; cell cell interaction; cryptosporidiosis; diarrhea; gastrointestinal infection; laboratory mouse; laboratory rabbit; malabsorption; monoclonal antibody; passive immunization; pathology; protozoal antigen; protozoal vaccine; surface antigens

Cryptosporidium parvum is the most common single infectious cause of diarrhea in AIDS patients (AIDS-associated diarrhea). Unfortunately, the infection has failed to respond to a large variety of treatment regimens, with the possible exception of a limited response to spiramycin and a controversial effect of bovine milk antibody in some patients. The basic biology and pathogenic mechanisms involved in the interaction between the parasite and the intestinal epithelium is poorly understood, and the mechanism of the diarrhea itself is unknown, hence it has been impossible to develop rational intervention or prevention strategies. It is unlikely that significant progress can be made without basic studies to understand the mechanisms of pathogenesis of this most important intestinal manifestation of AIDS. In this project we intend to do just this, by examining the surface of oocysts and sporozoites of C. parvum for the presence of antigenic determinants that may allow classification of isolates into subgroups based on antigens and clinical virulence in the host, to identify surface components that may be involved in parasite recognition of the intestinal cell and in the invasion of the enterocyte, to determine the impact of polyclonal or monoclonal antibody to specific surface constituents of the organism on attachment and/or invasion of the enterocyte, to search for sugar specific binding mechanisms in this interaction, to investigate the chemical nature of the cyst wall and to obtain clues to the biochemistry of encystation, and to determine the secretory immune response to the organism. Organisms will be obtained from human AIDS patients with chronic C. parvum infection, amplified by transmission to young calves to supply stocks of oocysts for study, monoclonal and polyclonal antibodies will be developed in mice and rabbits immunized with crude and purified antigens, assays for attachment invasion will be set up or developed for the purpose, and pathogenic properties of the organism will be evaluated using in vivo small animal models and in vitro systems designed to reveal specific characteristics of the relevant cell-cell interactions. The ultimate goal is to determine the immunogens to be used in a vaccine for active or passive immunization.

隐孢子虫是最常见的单一传染性 艾滋病患者腹泻的原因（艾滋病相关性腹泻）。 不幸的是，感染没有对大规模的 各种治疗方案，可能的例外是 对螺旋霉素的反应有限， 牛奶抗体在一些病人。 基础生物学和 致病机制涉及的相互作用， 寄生虫和肠上皮细胞知之甚少， 腹泻本身的机制是未知的，因此它有 无法制定合理的干预或预防措施 战略布局 不太可能取得重大进展 如果没有基本的研究来了解 这一最重要的肠道表现的发病机制 艾滋病 在这个项目中，我们打算这样做，通过检查 卵囊和子孢子的表面。小的存在， 抗原决定簇，可能允许分离株的分类 根据宿主中的抗原和临床毒力分为亚组， 以确定可能与寄生虫有关的表面成分， 肠细胞的识别和在入侵的 肠上皮细胞，以确定多克隆或单克隆 抗体的特定表面成分的生物体上 附着和/或侵入肠上皮细胞，以寻找糖 在这种相互作用的具体结合机制，研究 化学性质的囊肿壁，并获得线索， 包囊形成的生物化学，并确定 对生物体的免疫反应。 将获得微生物 从人类艾滋病患者慢性C.细小病毒感染， 通过传播给幼仔来扩大， 卵囊研究，单克隆和多克隆抗体将 在用粗品和纯化的 抗原，将建立用于附着入侵的测定，或 开发的目的，和致病特性的 将使用体内小动物模型评价微生物， 体外系统旨在揭示特定的特征， 相关的细胞间相互作用 最终目标是确定 用于主动或被动免疫的疫苗中的免疫原 次免疫

项目成果

Identification and partial purification of a lectin on the surface of the sporozoite of Cryptosporidium parvum.

小隐孢子虫子孢子表面凝集素的鉴定和部分纯化。

• 发表时间: 1992
• 期刊: The Journal of parasitology
• 作者: Thea,DM;Pereira,ME;Kotler,D;Sterling,CR;Keusch,GT
• 通讯作者: Keusch,GT