Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors.
Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors.
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DOI：
10.1038/nature24994
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发表时间：
2017-12-07
期刊：
影响因子：
64.8
通讯作者：
Arase H
中科院分区：
文献类型：
--
作者：
Saito F;Hirayasu K;Satoh T;Wang CW;Lusingu J;Arimori T;Shida K;Palacpac NMQ;Itagaki S;Iwanaga S;Takashima E;Tsuboi T;Kohyama M;Suenaga T;Colonna M;Takagi J;Lavstsen T;Horii T;Arase H
疟疾是影响人类的最严重传染病之一，每年造成大约50万人死亡。恶性疟原虫是大多数危及生命的疟疾病例的病原体。获得性疟疾免疫是低效的，即使在反复接触恶性疟原虫之后也是如此；恶性疟原虫的免疫调节机制仍不清楚。在这里，我们表明恶性疟原虫使用免疫抑制受体进行免疫逃避。RIFINs是一个多态多基因家族的产物，每个寄生虫基因组大约包含150-200个基因，在感染红细胞表面表达。我们发现RIFINs的一个亚群与白细胞免疫球蛋白样受体B1 （LILRB1）或白细胞相关免疫球蛋白样受体1 （LAIR1）结合。结合lilrb1的RIFINs抑制表达lilrb1的B细胞和NK细胞的活化。此外，LILRB1与从疟疾患者中分离的恶性疟原虫感染红细胞之间的相互作用与严重疟疾有关，尽管需要进行更大样本量的扩展研究来证实这一发现。这些结果表明，恶性疟原虫获得了多个RIFINs，通过靶向免疫抑制受体来逃避宿主免疫系统。
Malaria is among the most serious infectious diseases affecting humans, accounting for approximately half a million deaths annually. Plasmodium falciparum is the causative agent of most life-threatening malaria cases. Acquired immunity to malaria is inefficient, even after repeated exposures to P. falciparum; immune regulatory mechanisms employed by P. falciparum remain largely unclear. Here, we show that P. falciparum uses immune inhibitory receptors for immune evasion. RIFINs, products of a polymorphic multigene family comprising approximately 150–200 genes per parasite genome, are expressed on the surface of infected erythrocytes. We found that a subset of RIFINs binds to either leucocyte immunoglobulin-like receptor B1 (LILRB1) or leucocyte-associated immunoglobulin-like receptor 1 (LAIR1). LILRB1-binding RIFINs inhibited activation of LILRB1-expressing B cells and NK cells. Furthermore, interactions between LILRB1 and P. falciparum-infected erythrocytes isolated from malaria patients were associated with severe malaria, although an extended study with larger sample sizes is required to confirm the findings. These results suggest that P. falciparum has acquired multiple RIFINs to evade the host immune system by targeting immune inhibitory receptors.
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影响因子：
3.7
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