Centre for Immunology and Infection, Department of Biology/Hull York Medical School, University of York, Heslington, York, UK.
Parasite Immunol. 2013 Sep-Oct;35(9-10):283-94. doi: 10.1111/pim.12046.
Trypanosoma brucei are extracellular kinetoplastid parasites transmitted by the blood-sucking tsetse fly. They are responsible for the fatal disease human African trypanosomiasis (HAT), also known as sleeping sickness. In late-stage infection, trypanosomes cross the blood-brain barrier (BBB) and invade the central nervous system (CNS) invariably leading to coma and death if untreated. There is no available vaccine and current late-stage HAT chemotherapy consists of either melarsoprol, which is highly toxic causing up to 8% of deaths, or nifurtimox-eflornithine combination therapy (NECT), which is costly and difficult to administer. There is therefore an urgent need to identify new late-stage HAT drug candidates. Here, we review how current imaging tools, ranging from fluorescent confocal microscopy of live immobilized cells in culture to whole-animal imaging, are providing insight into T. brucei biology, parasite-host interplay, trypanosome CNS invasion and disease progression. We also consider how imaging tools can be used for candidate drug screening purposes that could lead to new chemotherapies.
布氏锥虫是通过吸血采采蝇传播的细胞外动基体寄生虫。它们是导致致命疾病——人类非洲锥虫病(又称昏睡病)的罪魁祸首。在晚期感染中,锥虫穿过血脑屏障(BBB)并侵入中枢神经系统(CNS),如果不治疗,通常会导致昏迷和死亡。目前尚无可用的疫苗,晚期 HAT 的化疗方法主要有两种,一是毒性很强的美拉胂醇,导致多达 8%的死亡率;二是依氟鸟氨酸-硝呋莫司联合疗法(NECT),但该疗法费用高且给药困难。因此,迫切需要确定新的晚期 HAT 药物候选物。本文综述了从培养中固定的活细胞的荧光共聚焦显微镜到全动物成像等现有成像工具如何为了解布氏锥虫生物学、寄生虫与宿主相互作用、锥虫对中枢神经系统的入侵和疾病进展提供了新的视角。我们还探讨了成像工具如何用于候选药物筛选,这可能会带来新的化疗方法。