IMMUNE REGULATION IN TOXOPLASMOSIS AND OTHER OPPORTUNISTIC INFECTIONS

弓形体病和其他机会性感染的免疫调节

• 批准号: 6160649
• 负责人: A SHER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6160649
• 关键词: HIV infections; Mycobacterium avium; Toxoplasma gondii; cellular immunity; dendritic cells; enzyme linked immunosorbent assay; gene induction /repression; histopathology; host organism interaction; immunofluorescence technique; immunoregulation; interleukin 12; laboratory mouse; opportunistic infections; protozoal antigen; toxoplasmosis; transcription factor; tumor necrosis factor alpha

The overall aim of this project is to analyze the immune response to Toxoplasma gondii and other intracellular opportunistic pathogens in order to define pathways of host resistance and their regulation. By so doing, we hope to design strategies for intervention against these infections in immunocompromised individuals. A secondary goal is to study the effects of the same pathogens on HIV-1 progression and to define the mechanisms involved. Significant progress was achieved this year in the following areas: 1) Identification of the dendritic cell as a major source of early T. gondii- induced IL-12. Cell fractionation and in situ staining experiments demonstrated that dendritic cells are likely to be the first host cells to produce IL-12 following T. gondii infection. 2) Identification of a novel transcription factor necessary for IL-12-dependent host resistance to T. gondii. The transcription factor ICSBP was shown to be required for control of T. gondii infection and to function by regulating the initial IL-12 response to the parasite. 3) Discovery of a latent form of T. gondii induced by vaccination. Immunization of mice with a tachyzoite extract plus IL-12 protected the animals from lethal challenge with a virulent strain. Nevertheless, the brains of these mice were found to contain latent parasite forms distinct from classical tissue cysts. 4) Development of a combined IL-12/antibiotic protocol for treatment of M. avium infection in vivo. Co-administration of IL-12 was shown to markedly enhance the efficacy of drug therapy of M. avium infections in mice.

该项目的总体目标是分析免疫反应， 弓形虫和其他细胞内机会致病菌 以确定宿主抗性的途径及其调节。通过这样 我们希望设计出针对这些问题的干预策略， 免疫力低下的人感染。第二个目标是 研究相同病原体对HIV-1进展的影响， 确定所涉及的机制。 今年在以下领域取得了重大进展： 1)树突状细胞作为早期T细胞主要来源的鉴定。 弓形虫诱导的IL-12。 细胞分级和原位染色 实验表明，树突状细胞可能是第一个 宿主细胞在T.弓形虫感染 2)一种新的转录因子的鉴定 IL-12依赖性宿主对T.刚地。转录因子 ICSBP是控制T.弓形虫感染和 通过调节IL-12对寄生虫的初始反应来发挥作用。 3)发现了T.接种疫苗诱发的弓形虫。 用速殖子提取物加IL-12免疫小鼠， 动物免受致命的攻击与有毒菌株。但 发现这些小鼠的大脑含有潜伏的寄生虫形式， 与典型的组织囊肿不同。 4)IL-12/抗生素联合治疗方案的开发 分枝体内感染禽流感病毒。IL-12的联合给药显示， 显著提高M.鸟类感染 对小鼠