Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, 12, rue des Professeurs Jeener et Brachet, B-6041 Gosselies, Belgium.
Curr Opin Immunol. 2009 Oct;21(5):493-8. doi: 10.1016/j.coi.2009.05.024. Epub 2009 Jun 24.
Humans are naturally resistant to infection by the African trypanosome prototype Trypanosoma brucei brucei, and only two variant clones of this parasite can avoid this innate immunity and cause sleeping sickness. The resistance to T. brucei is due to serum complexes associating apolipoprotein A-1 (apoA1) with two primate-specific proteins, apolipoprotein L-1 (apoL1) and haptoglobin-related protein (Hpr). We discuss recent advances on the respective functions of apoL1 and Hpr in this system. ApoL1 was found to share structural and functional similarities with proteins of the apoptotic Bcl2 family, and to kill trypanosomes through anionic pore formation in the lysosomal membrane of the parasite. In association with hemoglobin (Hb), Hpr was found to promote the binding of the trypanolytic complexes to a haptoglobin (Hp)-Hb receptor of the trypanosome surface, hereby facilitating the internalization of apoL1. Hpr or apoL1 deficiency respectively leads to the reduction or abolishment of human protection against T. brucei.
人类天生对非洲锥虫原型品系布氏锥虫具有抵抗力，只有这种寄生虫的两个变体克隆能够逃避这种先天免疫并引起昏睡病。对 T. brucei 的抗性归因于与载脂蛋白 A-1（apoA1）结合的血清复合物与两种灵长类动物特异性蛋白，载脂蛋白 L-1（apoL1）和触珠蛋白相关蛋白（Hpr）。我们讨论了 apoL1 和 Hpr 在该系统中的各自功能的最新进展。发现 apoL1 与凋亡 Bcl2 家族的蛋白质具有结构和功能相似性，并通过寄生虫溶酶体膜中的阴离子孔形成杀死锥虫。与血红蛋白（Hb）结合后，Hpr 被发现促进了 trypanolytic 复合物与锥虫表面的触珠蛋白（Hp）-Hb 受体的结合，从而促进了 apoL1 的内化。Hpr 或 apoL1 缺乏分别导致人类对 T. brucei 的保护减少或消除。
