Department of the Pathogenic Biology, The Third Military Medical University, Chongqing 400038, PR China.
Exp Parasitol. 2011 Jan;127(1):52-7. doi: 10.1016/j.exppara.2010.06.032. Epub 2010 Jul 1.
The antimalarial drug nitroquine is not only an effective antimalarial drug, it is also able to induce the melanization of Plasmodium species. However, the molecular mechanisms of the recognition reaction induced by this drug remain unclear. Silencing of thioester-containing protein-1 (TEP1) significantly compromised the ability of Anopheles gambiae to melanize the Plasmodium, leading to investigation of the involvement of A. stephensi TEP1 in melanization induced by nitroquine. This study shows that (1) binding of AsTEP1 to oocysts, especially melanized oocysts, (2) after ingestion of anti-AsTEP1 antibody, the melanization rate in antibody-treated mosquitoes are significantly lower than in control mosquito (p<0.05). The results suggest that nitroquine is able to induce Plasmodium recognition by TEP1, possibly triggering the resulting melanotic encapsulation. Further elucidation of the molecular mechanisms of mosquito immunity induced by antimalarial drugs will provide theoretical evidence for the use of antimalarial drugs, and a meaningful pathway for the design of novel antimalarial drugs.
抗疟药物硝喹不仅是一种有效的抗疟药物,还能够诱导疟原虫的黑化。然而,该药物诱导的识别反应的分子机制仍不清楚。硫酯蛋白-1(TEP1)的沉默显著削弱了冈比亚按蚊黑化疟原虫的能力,导致研究了斯蒂芬斯按蚊 TEP1 在硝喹诱导的黑化中的参与。本研究表明:(1)AsTEP1 与卵囊结合,特别是黑化卵囊结合;(2) 摄入抗 AsTEP1 抗体后,抗体处理蚊子中的黑化率明显低于对照蚊子(p<0.05)。结果表明,硝喹能够通过 TEP1 诱导疟原虫的识别,可能触发由此产生的黑化包封。进一步阐明抗疟药物诱导的蚊子免疫的分子机制将为抗疟药物的应用提供理论依据,并为设计新型抗疟药物提供有意义的途径。