Conserved mosquito/parasite interactions affect development of Plasmodium falciparum in Africa.
Conserved mosquito/parasite interactions affect development of Plasmodium falciparum in Africa.
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DOI：
10.1371/journal.ppat.1000069
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发表时间：
2008-05-16
期刊：
影响因子：
6.7
通讯作者：
Vlachou D
中科院分区：
文献类型：
--
作者：
Mendes AM;Schlegelmilch T;Cohuet A;Awono-Ambene P;De Iorio M;Fontenille D;Morlais I;Christophides GK;Kafatos FC;Vlachou D
在撒哈拉以南非洲的大部分地区，冈比亚按蚊是人类主要疟疾寄生虫恶性疟原虫的主要媒介。方便的实验室研究已经确定了蚊子基因，积极或消极地影响模式啮齿动物寄生虫，伯氏疟原虫的发育周期。在这里，我们使用转录谱和反向遗传学来探索是否五个不同的蚊子基因调节伯氏疟原虫的发展也与A。冈比亚/恶性疟原虫的相互作用在半自然条件下，使用该寄生虫和地理上相关的蚊子的现场分离物。我们检测到这些基因对两种寄生虫的转录反应大致相似，但不完全相同。基因沉默建立了两个基因同样影响两种寄生虫：感染受到细胞内局部肌动蛋白细胞骨架动力学激活剂WASP的阻碍，但受到血淋巴脂质转运蛋白ApoII/I的促进。由于伯氏疟原虫不是A.冈比亚，这些数据表明，这些基因的影响并没有急剧改变的不断相互作用和共同进化的A。gambiae和恶性疟原虫;这一结论使我们能够使用一套遗传工具和感染测定法在实验室模型系统中进一步研究这两种基因的作用模式。我们发现，这两个基因的作用在寄生虫的发育过渡从动合子卵囊的中肠入侵的水平。ApoII/I还影响卵囊发育的早期阶段。这些是第一个蚊子基因，其对恶性疟原虫现场分离株的显着影响已通过直接实验建立。重要的是，他们验证了半野外人类疟疾传播的寄生虫拮抗剂和激动剂的概念。疟疾是一种由蚊子传播的寄生虫传染病。它影响到世界一半的人口，每年造成100万至300万人死亡，其中绝大多数是撒哈拉以南非洲5岁以下的儿童。在那里，最致命的寄生虫是恶性疟原虫，其最重要的媒介是冈比亚按蚊。本研究首次鉴定出特异性A.冈比亚疟原虫基因，这些基因明显调节了非洲疟疾患者中传播的恶性疟原虫寄生虫对蚊子感染的密度。这些基因在蚊子脂质转运和细胞内肌动蛋白细胞骨架动力学中起作用，并分别作为寄生虫卵动素到卵囊发育转变的激动剂和拮抗剂。重要的是，我们的研究验证了支持或阻碍寄生虫发育的蚊子基因的概念，这是我们之前使用实验室模型系统定义的概念。因此，这项工作对理解自然传播条件下有意义的蚊子/寄生虫相互作用做出了重大贡献。
In much of sub-Saharan Africa, the mosquito Anopheles gambiae is the main vector of the major human malaria parasite, Plasmodium falciparum. Convenient laboratory studies have identified mosquito genes that affect positively or negatively the developmental cycle of the model rodent parasite, P. berghei. Here, we use transcription profiling and reverse genetics to explore whether five disparate mosquito gene regulators of P. berghei development are also pertinent to A. gambiae/P. falciparum interactions in semi-natural conditions, using field isolates of this parasite and geographically related mosquitoes. We detected broadly similar albeit not identical transcriptional responses of these genes to the two parasite species. Gene silencing established that two genes affect similarly both parasites: infections are hindered by the intracellular local activator of actin cytoskeleton dynamics, WASP, but promoted by the hemolymph lipid transporter, ApoII/I. Since P. berghei is not a natural parasite of A. gambiae, these data suggest that the effects of these genes have not been drastically altered by constant interaction and co-evolution of A. gambiae and P. falciparum; this conclusion allowed us to investigate further the mode of action of these two genes in the laboratory model system using a suite of genetic tools and infection assays. We showed that both genes act at the level of midgut invasion during the parasite's developmental transition from ookinete to oocyst. ApoII/I also affects the early stages of oocyst development. These are the first mosquito genes whose significant effects on P. falciparum field isolates have been established by direct experimentation. Importantly, they validate for semi-field human malaria transmission the concept of parasite antagonists and agonists. Malaria is a parasitic infectious disease transmitted by mosquitoes. It impacts half the population of the world and kills 1 to 3 million people every year, the vast majority of whom are children aged below 5 in sub-Saharan Africa. There, the deadliest parasite is Plasmodium falciparum and its most important vector is the mosquito Anopheles gambiae. This study identifies for the first time specific A. gambiae genes that demonstrably regulate the density of mosquito infection by P. falciparum parasites circulating in malaria patients in Africa. These genes function in mosquito lipid transport and intracellular actin cytoskeleton dynamics, and act as an agonist and an antagonist, respectively, of the parasite ookinete-to-oocyst developmental transition. Importantly, our study validates for P. falciparum the concept of mosquito genes that support or hinder parasite development, a concept that we defined previously using a laboratory model system. Thus, the work constitutes a major contribution to understanding meaningful mosquito/parasite interactions in natural transmission conditions.
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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：
9.6
作者：
Baton, LA;Ranford-Cartwright, LC
通讯作者：
Ranford-Cartwright, LC
影响因子：
7.7
作者：
Michel, K;Budd, A;Kafatos, FC
通讯作者：
Kafatos, FC
影响因子：
56.9
作者：
Christophides, GK;Zdobnov, E;Kafatos, FC
通讯作者：
Kafatos, FC
DOI：
10.1073/pnas.0504950102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Meister, S;Kanzok, SM;Zheng, LB
通讯作者：
Zheng, LB