The major yolk protein vitellogenin interferes with the anti-plasmodium response in the malaria mosquito Anopheles gambiae.
The major yolk protein vitellogenin interferes with the anti-plasmodium response in the malaria mosquito Anopheles gambiae.
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DOI：
10.1371/journal.pbio.1000434
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发表时间：
2010-07-20
期刊：
影响因子：
9.8
通讯作者：
Marois E
中科院分区：
文献类型：
--
作者：
Rono MK;Whitten MM;Oulad-Abdelghani M;Levashina EA;Marois E
疟疾蚊子的功能基因分析揭示了支撑有效繁殖和抗寄生虫反应之间权衡的分子。当疟疾感染者吸食血粉时，雌性冈比亚按蚊（人类疟疾的主要传播媒介）会获得营养物质，从而激活卵巢中的卵子发育（卵子发生）。同时，他们也会感染疟疾寄生虫。在穿过蚊子中肠上皮时，入侵的动动疟原虫会遇到主要由蚊子血细胞控制的强大的先天免疫反应。蚊子繁殖和免疫的伴随过程是否相互影响仍然存在争议。在这里，我们发现向成熟的蚊子卵母细胞输送营养的蛋白质会干扰抗寄生虫反应。脂蛋白 (Lp) 和卵黄蛋白原 (Vg) 这两种营养转运蛋白可降低抗寄生虫因子 TEP1 的杀虫效率。在缺乏任一营养转运蛋白的情况下，TEP1 与动动物表面的结合变得更加有效。我们还表明，Lp 是 Vg 正常表达以及卵囊阶段疟原虫后期发育所必需的。此外，我们的结果揭示了 Cactus/REL1/REL2 信号盒对 Vg 表达的抑制作用，但对 Lp 的表达没有抑制作用。我们揭示了在多个层面上连接生殖和免疫的分子联系，并为这两个过程之间长期怀疑的权衡提供了分子基础。疟疾每年夺走近 100 万婴儿的生命，给非洲和其他热带地区带来重大的社会经济负担。与此同时，疟疾寄生虫与其按蚊媒介之间的详细生物相互作用在很大程度上仍然是个谜。我们所知道的是，大多数疟疾寄生虫通常会被蚊子的免疫反应消除。蚊子通过吸食充满寄生虫的血液而意外受到感染，但这掩盖了血液的主要功能是为昆虫卵巢中的卵子发育提供营养。我们发现，将血液中的营养物质输送给成熟卵所涉及的分子过程会降低蚊子免疫系统杀死寄生虫的效率。相反，将免疫系统设定为最大杀灭寄生虫能力的分子途径会阻碍蚊子卵的有效发育。我们的结果揭示了支撑生殖与免疫之间权衡这一例子的一些分子，这一概念长期以来一直引起生物学家的兴趣。
Functional gene analysis in malaria mosquitoes reveals molecules underpinning the trade-off between efficient reproduction and the antiparasitic response. When taking a blood meal on a person infected with malaria, female Anopheles gambiae mosquitoes, the major vector of human malaria, acquire nutrients that will activate egg development (oogenesis) in their ovaries. Simultaneously, they infect themselves with the malaria parasite. On traversing the mosquito midgut epithelium, invading Plasmodium ookinetes are met with a potent innate immune response predominantly controlled by mosquito blood cells. Whether the concomitant processes of mosquito reproduction and immunity affect each other remains controversial. Here, we show that proteins that deliver nutrients to maturing mosquito oocytes interfere with the antiparasitic response. Lipophorin (Lp) and vitellogenin (Vg), two nutrient transport proteins, reduce the parasite-killing efficiency of the antiparasitic factor TEP1. In the absence of either nutrient transport protein, TEP1 binding to the ookinete surface becomes more efficient. We also show that Lp is required for the normal expression of Vg, and for later Plasmodium development at the oocyst stage. Furthermore, our results uncover an inhibitory role of the Cactus/REL1/REL2 signaling cassette in the expression of Vg, but not of Lp. We reveal molecular links that connect reproduction and immunity at several levels and provide a molecular basis for a long-suspected trade-off between these two processes. Malaria annually claims the lives of almost 1 million infants and imposes a major socio-economic burden on Africa and other tropical regions. Meanwhile, the detailed biological interactions between the malaria parasite and its Anopheles mosquito vector remain largely enigmatic. What we do know is that the majority of malaria parasites are normally eliminated by the mosquito's immune response. Mosquitoes accidentally acquire an infection by sucking parasite-laden blood, but this belies the primary function of the blood in the provisioning of nutrients for egg development in the insect's ovaries. We have found that the molecular processes involved in delivering blood-acquired nutrients to maturing eggs diminish the efficiency of parasite killing by the mosquito immune system. Conversely, molecular pathways that set the immune system on its maximal capacity for parasite killing preclude the efficient development of the mosquito's eggs. Our results reveal some of the molecules that underpin this example of the trade-offs between reproduction and immunity, a concept that has long intrigued biologists.
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影响因子：
6.7
作者：
Habtewold T;Povelones M;Blagborough AM;Christophides GK
通讯作者：
Christophides GK
影响因子：
6.7
作者：
Dong Y;Aguilar R;Xi Z;Warr E;Mongin E;Dimopoulos G
通讯作者：
Dimopoulos G
影响因子：
32.4
作者：
Frolet, Cecile;Thoma, Martine;Levashina, Elena A.
通讯作者：
Levashina, Elena A.
DOI：
10.1073/pnas.0704967104
发表时间：
2007-07-10
影响因子：
11.1
作者：
Baxter, Richard H. G.;Chang, Chung-I;Deisenhofer, Johann
通讯作者：
Deisenhofer, Johann
影响因子：
5.8
作者：
Ahmed, AM;Hurd, H
通讯作者：
Hurd, H