Vector Immunogenomics and Infection Laboratory, Department of Life Sciences, Imperial College London, London, United Kingdom.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Sci Rep. 2017 Jul 20;7(1):6026. doi: 10.1038/s41598-017-05917-6.
Malaria is a mosquito-borne disease affecting millions of people every year. The rodent parasite Plasmodium berghei has served as a model for human malaria transmission studies and played a pivotal role in dissecting the mosquito immune response against infection. The 6-cysteine protein P47, known to be important for P. berghei female gamete fertility, is shown to serve a different function in Plasmodium falciparum, protecting ookinetes from the mosquito immune response. Here, we investigate the function of P. berghei P47 in Anopheles gambiae mosquito infections. We show that P47 is expressed on the surface of both female gametocytes and ookinetes where it serves distinct functions in promoting gametocyte-to-ookinete development and protecting ookinetes from the mosquito complement-like response, respectively. The latter function is essential, as ookinetes lacking P47 are targeted for killing while traversing the mosquito midgut cells and eliminated upon exposure to hemolymph proteins of the complement-like system. Silencing key factors of the complement-like system restores oocyst development and disease transmission to rodent hosts. Our data establish a dual role of P. berghei P47 in vivo and reinforce the use of this parasite to study the impact of the mosquito immune response on human malaria transmission.
疟疾是一种由蚊子传播的疾病，每年影响数百万人。啮齿动物寄生虫疟原虫已被用作人类疟疾传播研究的模型，并在解析蚊子对感染的免疫反应方面发挥了关键作用。已知对疟原虫雌性配子体育性很重要的 6 半胱氨酸蛋白 P47 在恶性疟原虫中发挥不同的功能，保护动合子免受蚊子的免疫反应。在这里，我们研究了疟原虫 P47 在冈比亚按蚊感染中的功能。我们表明，P47 表达在雌性配子体和动合子的表面，在促进配子体向动合子发育和保护动合子免受蚊子补体样反应方面分别发挥不同的功能。后一个功能是必不可少的，因为缺乏 P47 的动合子在穿过蚊子中肠细胞时会被靶向杀死，并在暴露于补体样系统的血淋巴蛋白时被消除。沉默补体样系统的关键因素可以恢复卵囊发育并将疾病传播给啮齿动物宿主。我们的数据确立了 P. berghei P47 在体内的双重作用，并加强了利用这种寄生虫来研究蚊子免疫反应对人类疟疾传播的影响。
