Plasmodium falciparum Uses gC1qR/HABP1/p32 as a Receptor to Bind to Vascular Endothelium and for Platelet-Mediated Clumping

The ability of Plasmodium falciparum–infected red blood cells (IRBCs) to bind to vascular endothelium, thus enabling sequestration in vital host organs, is an important pathogenic mechanism in malaria. Adhesion of P. falciparum IRBCs to platelets, which results in the formation of IRBC clumps, is another cytoadherence phenomenon that is associated with severe disease. Here, we have used in vitro cytoadherence assays to demonstrate, to our knowledge for the first time, that P. falciparum IRBCs use the 32-kDa human protein gC1qR/HABP1/p32 as a receptor to bind to human brain microvascular endothelial cells. In addition, we show that P. falciparum IRBCs can also bind to gC1qR/HABP1/p32 on platelets to form clumps. Our study has thus identified a novel host receptor that is used for both adhesion to vascular endothelium and platelet-mediated clumping. Given the association of adhesion to vascular endothelium and platelet-mediated clumping with severe disease, adhesion to gC1qR/HABP1/p32 by P. falciparum IRBCs may play an important role in malaria pathogenesis.

恶性疟原虫（Plasmodium falciparum）感染的红细胞（infected red blood cells，下文简称IRBCs）与血管内皮结合、进而在宿主重要器官中形成滞留的能力，是疟疾的重要致病机制。恶性疟原虫感染的红细胞与血小板结合并形成红细胞团块的现象，是另一种与重症疟疾相关的细胞黏附现象。本研究通过体外细胞黏附实验，据我们所知首次证实，恶性疟原虫感染的红细胞可借助32 kDa的人类蛋白gC1qR/HABP1/p32作为受体，与人脑微血管内皮细胞结合。此外，本研究还发现，恶性疟原虫感染的红细胞可结合血小板表面的gC1qR/HABP1/p32，进而形成团块。本研究据此鉴定出一种新型宿主受体，该受体同时介导恶性疟原虫感染红细胞与血管内皮的黏附，以及血小板介导的红细胞团块形成。鉴于血管内皮黏附与血小板介导的红细胞团块形成均与重症疟疾相关，恶性疟原虫感染的红细胞通过结合gC1qR/HABP1/p32实现黏附的过程，可能在疟疾致病过程中发挥重要作用。