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非洲锥虫病的发病机制

The Pathogenesis of African Trypanosomiasis.

作者信息

Pays Etienne, Radwanska Magdalena, Magez Stefan

机构信息

Laboratory of Molecular Parasitology, Université Libre de Bruxelles, Gosselies, Belgium; email:

Laboratory for Biomedical Research, Ghent University Global Campus, Incheon, South Korea.

出版信息

Annu Rev Pathol. 2023 Jan 24;18:19-45. doi: 10.1146/annurev-pathmechdis-031621-025153. Epub 2022 Sep 2.

Abstract

African trypanosomes are bloodstream protozoan parasites that infect mammals including humans, where they cause sleeping sickness. Long-lasting infection is required to favor parasite transmission between hosts. Therefore, trypanosomes have developed strategies to continuously escape innate and adaptive responses of the immune system, while also preventing premature death of the host. The pathology linked to infection mainly results from inflammation and includes anemia and brain dysfunction in addition to loss of specificity and memory of the antibody response. The serum of humans contains an efficient trypanolytic factor, the membrane pore-forming protein apolipoprotein L1 (APOL1). In the two human-infective trypanosomes, specific parasite resistance factors inhibit APOL1 activity. In turn, many African individuals express APOL1 variants that counteract these resistance factors, enabling them to avoid sleeping sickness. However, these variants are associated with chronic kidney disease, particularly in the context of virus-induced inflammation such as coronavirus disease 2019. Vaccination perspectives are discussed.

摘要

非洲锥虫是寄生于血液中的原生动物寄生虫,可感染包括人类在内的哺乳动物,引发昏睡病。需要长期感染才有利于寄生虫在宿主间传播。因此,锥虫已发展出多种策略,以持续逃避免疫系统的先天性和适应性反应,同时还能防止宿主过早死亡。与感染相关的病理主要由炎症引起,除了抗体反应失去特异性和记忆外,还包括贫血和脑功能障碍。人类血清中含有一种高效的锥虫溶解因子,即膜孔形成蛋白载脂蛋白L1(APOL1)。在两种可感染人类的锥虫中,特定的寄生虫抗性因子会抑制APOL1的活性。反过来,许多非洲人表达的APOL1变体可抵消这些抗性因子,使他们能够避免感染昏睡病。然而,这些变体与慢性肾病有关,尤其是在病毒诱导的炎症(如2019冠状病毒病)的情况下。文中还讨论了疫苗接种的前景。

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