The N-Terminal Region of Plasmodium falciparum MSP10 Is a Target of Protective Antibodies in Malaria and Is Important for PfGAMA/PfMSP10 Interaction
The N-Terminal Region of Plasmodium falciparum MSP10 Is a Target of Protective Antibodies in Malaria and Is Important for PfGAMA/PfMSP10 Interaction
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DOI：
10.3389/fimmu.2019.02669
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发表时间：
2019-11-20
影响因子：
7.3
通讯作者：
Takashima, Eizo
中科院分区：
文献类型：
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作者：
Nagaoka, Hikaru;Kanoi, Bernard N.;Takashima, Eizo
疟疾的临床表现主要是由于疟原虫在红细胞内发育。恶性疟原虫裂殖子是血液期寄生虫的侵入形式，以复杂但快速的过程侵入人类红细胞。这种多步骤的进展涉及寄生虫和人类宿主蛋白质之间的相互作用。在这里，我们表明，针对疫苗抗原PfGAMA的抗体与PfMSP 10共免疫沉淀。通过表面等离子体共振分析验证了这种相互作用是直接的。然后，我们证明了PfMSP 10抗体对培养的寄生虫具有生长抑制活性，PfMSP 10 R1区域是其与PfGAMA相互作用的关键靶点。我们还观察到PfMSP 10 R1区域在非洲田间分离株中高度保守。最后，我们表明，在乌干达北方疟疾流行区的儿童中，高水平的PfMSP 10 R1抗体与临床疟疾风险降低有关。总之，这些发现首次提供了PfGAMA/PfMSP 10相互作用在红细胞侵袭中的重要作用的功能背景，并揭示了用于减弱恶性疟原虫裂殖子侵袭的新型无性血液阶段疟疾疫苗靶标。
Clinical manifestation of malaria is mainly due to intra-erythrocytic development of Plasmodium parasites. Plasmodium falciparum merozoites, the invasive form of the blood-stage parasite, invade human erythrocytes in a complex but rapid process. This multi-step progression involves interactions between parasite and human host proteins. Here we show that antibodies against a vaccine antigen, PfGAMA, co-immunoprecipitate with PfMSP10. This interaction was validated as direct by surface plasmon resonance analysis. We then demonstrate that antibodies against PfMSP10 have growth inhibitory activity against cultured parasites, with the region PfMSP10 R1 that is critical for its interaction with PfGAMA being the key target. We also observe that the PfMSP10 R1 region is highly conserved among African field isolates. Lastly, we show that high levels of antibodies against PfMSP10 R1 associate with reduced risk to clinical malaria in children resident in a malaria endemic region in northern Uganda. Put together, these findings provide for the first time the functional context of the important role of PfGAMA/PfMSP10 interaction in erythrocyte invasion and unveil a novel asexual blood-stage malaria vaccine target for attenuating P. falciparum merozoite invasion.