TOXOPLASMA GONDII--DIAGNOSIS AND PREVENTION IN AIDS

描述（改编自摘要）：这一竞争的总体目标 更新项目是为了更全面地了解寄生虫：宿主细胞界面 从而定义可用于目标控制的关键要素 艾滋病患者的弓形虫病。 上一个供资期的工作使 证明了一种特定的寄生虫配体：宿主细胞受体 相互作用发生在入侵过程之前。 这里提出的工作 是为了鉴定这种不受调节的宿主细胞受体 在细胞周期的S期。 该基因将从一个 cDNA文库，并与其他已知的真核受体蛋白进行比较。 的 受体基因将在昆虫细胞中表达，对T.弓形虫 感染，以及寄生虫和受体之间的相互作用研究。 在 此外，受体将过表达或从其他细胞中去除， 真核细胞 SAG1将以N表示。犬齿检查 宿主细胞受体对SAG1的特异性。 第二个目的是探索是否有其他寄生虫附着配体， 特别是MIC蛋白，在附着过程中很重要， 激活人单核细胞。 最近的观察表明MIC1参与其中 在寄生虫附着和入侵人类之间的界面 单核细胞 建议进行研究以确定MIC 1（可能还有MIC 2）是否 3）通过对MIC的功能分析， 蛋白质在人体内侵入和内化过程中的作用 单核细胞 MIC刺激单核细胞的天然免疫应答 宿主细胞受体的结合将通过测定 激活两条信号转导通路，诱导细胞因子， 已知的下调宿主淋巴细胞的可溶性因子的产生 增殖 旨在干扰人际依恋的策略 寄生虫配体和宿主细胞受体应该提供新的靶点， 开发新的治疗药物来治疗这种机会性的 感染艾滋病的人。

DESCRIPTION (adapted from the Abstract): The overall aim of this competing renewal project is to understand more fully the parasite:host cell interface and, thereby, define key elements that could be used for targets to control toxoplasmosis in AIDS patients. Work in the last funding period has allowed the demonstration that a specific parasite ligand:host cell receptor interaction occurs prior to the process of invasion. The work proposed here is for the identification of this host cell receptor that is unregulated during the S phase of the cell cycle. This gene will be isolated from a cDNA library and compared to other known eukaryotic receptor proteins. The receptor gene will be expressed in insect cells, nonpermissive for T. gondii infection, and the interaction between parasite and receptor studied. In addition, the receptor will be overexpressed or removed from other eukaryotic cells. SAG1 will be expressed in N. caninum to examine the specificity of the host cell receptor for SAG1. The second aim is to explore whether other parasite attachment ligands, in particular the MIC proteins, are important in the process of attachment and activation of human monocytes. Recent observations suggest MIC1 is involved in the interface between parasite attachment and invasion of human monocytes. Studies are proposed to determine whether MIC1 (and perhaps MIC2 and 3) are involved in this process by functional analysis of the MIC protein during the process of invasion and internalization in human monocytic cells. The innate immune response of monocytes stimulated by MIC engagement of the host cell receptor will be evaluated by determining the activation of two signal transduction pathways, induction of cytokines, and the production of a known soluble factor that downregulates host lymphoid proliferation. Strategies directed at interfering with attachment between parasite ligands and host cell receptor(s) should provide novel targets for the development of new therapeutic agents for treating this opportunistic infection in those afflicted with AIDS.