Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Schools of Biology and Chemistry Biomedical Sciences Research Complex, The North Haugh, The University, St. Andrews, Scotland, United Kingdom.
PLoS Negl Trop Dis. 2021 Oct 29;15(10):e0009912. doi: 10.1371/journal.pntd.0009912. eCollection 2021 Oct.
Malaria, a disease caused by Plasmodium parasites, remains a major threat to public health globally. It is the most common disease in patients with sleeping sickness, another parasitic illness, caused by Trypanosoma brucei. We have previously shown that a T. brucei infection impairs a secondary P. berghei liver infection and decreases malaria severity in mice. However, whether this effect requires an active trypanosome infection remained unknown. Here, we show that Plasmodium liver infection can also be inhibited by the serum of a mouse previously infected by T. brucei and by total protein lysates of this kinetoplastid. Biochemical characterisation showed that the anti-Plasmodium activity of the total T. brucei lysates depends on its protein fraction, but is independent of the abundant variant surface glycoprotein. Finally, we found that the protein(s) responsible for the inhibition of Plasmodium infection is/are present within a fraction of ~350 proteins that are excreted to the bloodstream of the host. We conclude that the defence mechanism developed by trypanosomes against Plasmodium relies on protein excretion. This study opens the door to the identification of novel antiplasmodial intervention strategies.
疟疾是由疟原虫引起的疾病，仍然是全球公共卫生的主要威胁。它是昏睡病（另一种由布氏锥虫引起的寄生虫病）患者中最常见的疾病。我们之前已经表明，布氏锥虫感染会损害继发的伯氏疟原虫肝脏感染，并降低小鼠疟疾的严重程度。然而，这种效果是否需要一个活跃的锥虫感染仍然未知。在这里，我们表明，疟原虫肝脏感染也可以被先前感染布氏锥虫的小鼠的血清和这种动基体原生动物的总蛋白裂解物抑制。生化特性表明，总布氏锥虫裂解物的抗疟原虫活性取决于其蛋白质部分，但不依赖于丰富的表面变异糖蛋白。最后，我们发现，负责抑制疟原虫感染的蛋白质/蛋白质存在于宿主血液中分泌的约 350 种蛋白质的一个部分中。我们得出的结论是，锥虫针对疟原虫开发的防御机制依赖于蛋白质的分泌。这项研究为鉴定新的抗疟干预策略开辟了道路。
