IMMUNE REGULATION IN TOXOPLASMOSIS AND OTHER OPPORTUNISTIC INFECTIONS

这个项目的总体目标是分析免疫反应 弓形虫等细胞内条件致病菌 以确定寄主抗性的途径及其调控。是这样的 这样做，我们希望设计针对这些问题的干预策略 免疫功能受损个体的感染。次要目标是 研究相同病原体对HIV-1进展的影响 定义涉及的机制。 今年在以下方面取得了重大进展： 1)树突状细胞是早期分枝杆菌的主要来源。 贡地诱导的IL-12。细胞分离和原位染色 实验证明，树突状细胞很可能是第一个 弓形虫感染后宿主细胞产生IL-12。 2)鉴定了一个新的转录因子 依赖IL-12的寄主对弓形虫的抗性。转录因子 研究表明，控制弓形虫感染需要ICSBP。 通过调节对寄生虫的初始IL-12反应来发挥作用。 3)发现了一种疫苗诱导的潜伏型弓形虫。 速殖子提取物加IL-12免疫小鼠可保护小鼠 用一种致命的菌株使动物免受致命的挑战。尽管如此， 这些小鼠的大脑被发现含有潜伏的寄生虫形式 不同于经典的组织囊肿。 4)建立IL-12/抗生素联合治疗方案 体内感染禽类支原体的可能性。联合使用IL-12被证明是 显著提高禽类支原体感染的药物治疗效果 在老鼠身上。

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.