PDF(Pubmed)
Abstract：
Haptoglobin is a plasma protein of mammals that plays a crucial role in vascular homeostasis by binding free haemoglobin released from ruptured red blood cells. Trypanosoma brucei can exploit this by internalising haptoglobin-haemoglobin complex to acquire host haem. Here, we investigated the impact of haptoglobin deficiency (Hp-/-) on T. brucei brucei infection and the parasite´s capacity to internalise haemoglobin in a Hp-/- mouse model. The infected Hp-/- mice exhibited normal disease progression, with minimal weight loss and no apparent organ pathology, similarly to control mice. While the proteomic profile of mouse sera significantly changed in response to T. b. brucei, no differences in the infection response markers of blood plasma between Hp-/- and control Black mice were observed. Similarly, very few quantitative differences were observed between the proteomes of parasites harvested from Hp-/- and Black mice, including both endogenous proteins and internalised host proteins. While haptoglobin was indeed absent from parasites isolated from Hp-/-mice, haemoglobin peptides were unexpectedly detected in parasites from both Hp-/- and Black mice. Combined, the data support the dispensability of haptoglobin for haemoglobin internalisation by T. b. brucei during infection in mice. Since the trypanosomes knock-outs for their haptoglobin-haemoglobin receptor (HpHbR) internalised significantly less haemoglobin from Hp-/- mice compared to those isolated from Black mice, it suggests that T. b. brucei employs also an HpHbR-independent haptoglobin-mediated mode for haemoglobin internalisation. Our study reveals a so-far hidden flexibility of haemoglobin acquisition by T. b. brucei and offers novel insights into alternative haemoglobin uptake pathways.
摘要：
结合珠蛋白是哺乳动物的血浆蛋白,其通过结合从破裂的红细胞释放的游离血红蛋白而在血管内稳态中起关键作用。布鲁氏锥虫可以通过内化触珠蛋白-血红蛋白复合物来获取宿主血红素来利用这一点。这里,我们在Hp-/-小鼠模型中研究了结合珠蛋白缺乏(Hp-/-)对布氏杆菌感染的影响以及寄生虫内化血红蛋白的能力.感染的Hp-/-小鼠表现出正常的疾病进展，体重减轻最小，没有明显的器官病理学，与对照小鼠相似。而小鼠血清的蛋白质组学谱在响应T.b.brucei时显著改变，在Hp-/-和对照Black小鼠之间没有观察到血浆的感染反应标志物的差异。同样，从Hp-/-和Black小鼠收获的寄生虫的蛋白质组之间观察到很少的数量差异，包括内源蛋白和内化宿主蛋白。虽然从Hp-/-小鼠分离的寄生虫中确实不存在触珠蛋白，在来自Hp-/-和Black小鼠的寄生虫中意外地检测到血红蛋白肽。合并,数据支持结合珠蛋白在小鼠感染期间通过T.b.brucei进行血红蛋白内化的可分配性。由于锥虫敲除的结合珠蛋白-血红蛋白受体（HpHbR）内化的血红蛋白明显少于从Black小鼠分离的血红蛋白，这表明T.b.brucei也采用HpHbR非依赖性触珠蛋白介导的血红蛋白内化模式。我们的研究揭示了T.b.brucei获得血红蛋白的迄今为止隐藏的灵活性，并提供了对替代血红蛋白摄取途径的新颖见解。
