Transmission blocking immunity in the malaria non-vector mosquito Anopheles quadriannulatus species A.
Transmission blocking immunity in the malaria non-vector mosquito Anopheles quadriannulatus species A.
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DOI：
10.1371/journal.ppat.1000070
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发表时间：
2008-05-23
期刊：
影响因子：
6.7
通讯作者：
Christophides GK
中科院分区：
文献类型：
--
作者：
Habtewold T;Povelones M;Blagborough AM;Christophides GK
尽管在系统发育上与非洲人类疟疾的主要蚊媒冈比亚按蚊非常接近，但四环按蚊被认为不是媒介。了解媒介蚊子和非媒介蚊子之间的差异可以促进新型疟疾控制策略的制定。我们证明了 An. Quadriannulatus 对人类寄生虫恶性疟原虫以及啮齿动物寄生虫伯氏疟原虫的感染有很大的抵抗力。通过使用遗传学和反向遗传学，我们表明抗性是由数量遗传性状控制的，并通过蚊子中肠中动动子的裂解或黑化以及在蚊子发育的后续阶段杀死寄生虫来体现。编码两种富含亮氨酸的重复蛋白 LRIM1 和 LRIM2 以及含硫酯的蛋白 TEP1 的基因被认为在这些免疫反应中至关重要。它们的沉默完全消除了伯氏疟原虫黑化作用，并显着增加了卵囊的数量，从而改变了伯氏疟原虫的形态。使quadriannulatus变成高度宽容的寄生虫宿主。我们假设蚊子免疫系统是对疟疾自然抵抗的一个重要原因，利用蚊子的这种先天能力可能会带来控制疾病传播的新方法。疟疾是一种由蚊子传播的传染病，威胁着近一半的人口，每年导致 1 至 300 万人死亡。在撒哈拉以南非洲地区，绝大多数死亡发生在该地区，即使在密切相关的物种之间，蚊子传播疟疾的能力也存在很大差异。我们比较了疟疾寄生虫在两种密切相关的蚊子（一种媒介蚊子和一种非媒介蚊子）中发育的能力，发现非媒介蚊子在不同阶段杀死寄生虫，主要是当它们侵入蚊子中肠时。这是通过寄生虫清除来实现的，可能是通过中肠细胞的裂解和黑化来实现的，这两者都是蚊子免疫系统的反应。这种表型取决于可遗传和显性的特征，这些特征可以传递给媒介/非媒介蚊子杂交体。我们检查了蚊子免疫系统的特定组成部分是否会影响这些蚊子对感染的抵抗力。通过沉默三个免疫基因的活性，我们将耐药物种的蚊子转化为高度易感的。我们的结果表明，蚊子免疫系统可能会影响非媒介蚊子对疟疾的抵抗力。蚊子这种杀死疟疾寄生虫的先天能力可以在未来控制和最终根除这种疾病的综合努力中得到利用。
Despite being phylogenetically very close to Anopheles gambiae, the major mosquito vector of human malaria in Africa, Anopheles quadriannulatus is thought to be a non-vector. Understanding the difference between vector and non-vector mosquitoes can facilitate development of novel malaria control strategies. We demonstrate that An. quadriannulatus is largely resistant to infections by the human parasite Plasmodium falciparum, as well as by the rodent parasite Plasmodium berghei. By using genetics and reverse genetics, we show that resistance is controlled by quantitative heritable traits and manifested by lysis or melanization of ookinetes in the mosquito midgut, as well as by killing of parasites at subsequent stages of their development in the mosquito. Genes encoding two leucine-rich repeat proteins, LRIM1 and LRIM2, and the thioester-containing protein, TEP1, are identified as essential in these immune reactions. Their silencing completely abolishes P. berghei melanization and dramatically increases the number of oocysts, thus transforming An. quadriannulatus into a highly permissive parasite host. We hypothesize that the mosquito immune system is an important cause of natural refractoriness to malaria and that utilization of this innate capacity of mosquitoes could lead to new methods to control transmission of the disease. Malaria is a mosquito-borne infectious disease that threatens almost half of the human population and kills 1 to 3 million people every year. In sub-Saharan Africa, where the vast majority of deaths occur, the capacity of mosquitoes to transmit malaria varies greatly even between closely related species. We compared the ability of malaria parasites to develop in two very closely related mosquitoes, one vector and one non-vector, and found that non-vector mosquitoes kill parasites at various stages, predominantly when they invade the mosquito midgut. This is achieved by parasite clearance, possibly by lysis in the midgut cells and by melanization, both of which are reactions of the mosquito immune system. This phenotype depends on heritable and dominant traits that can be passed on to vector/non-vector mosquito hybrids. We examined whether specific components of the mosquito immune system affect the resistance of these mosquitoes to infection. By silencing the activity of three immunity genes, we transformed mosquitoes of the resistant species into highly susceptible. Our results suggest that the mosquito immune system may affect refractoriness to malaria in non-vector mosquitoes. This innate capacity of mosquitoes to kill malaria parasites could be utilized in future integrated efforts to control and ultimately eradicate the disease.
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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：
56.9
作者：
Riehle, MM;Markianos, K;Vernick, KD
通讯作者：
Vernick, KD
DOI：
10.1016/s0035-9203(98)90761-1
发表时间：
1998-03-01
影响因子：
2.2
作者：
Hunt, RH;Coetzee, M;Fettene, M
通讯作者：
Fettene, M
影响因子：
--
作者：
Pates, HV;Takken, W;Jamet, H
通讯作者：
Jamet, H
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