Acquisition of human plasminogen facilitates complement evasion by the malaria parasite Plasmodium falciparum

摘要

The tropical disease malaria claims more than 400,000 victims every year. Most deaths are due to infections with Plasmodium falciparum, the causative agent of malignant malaria [1]. Affected people particularly suffer from high fever, anemia, hemoglobinuria, and neurological dysfunctions, caused by the red blood cell (RBC)-infecting stages of the unicellular parasite. To avoid destruction by human complement, the parasites acquire complement regulators like factor H, which bind to the surface of the infected RBC [2,3]. In addition, the factor H-related protein FHR-1 is able to bind to infected RBCs, where it counteracts complement evasion [4]. Plasmodium falciparum is also able to acquire the plasma zymogen plasminogen (Plg) [5,6]. Mediated by the urokinase-type and tissue-type plasminogen activators uPA and tPA, Plg can be converted into the serine protease plasmin (Plm), which is involved in fibrin degradation but can also process complement factors such as C3 and C5 [7,8].