Engineered anopheles immunity to Plasmodium infection.
Engineered anopheles immunity to Plasmodium infection.
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DOI：
10.1371/journal.ppat.1002458
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发表时间：
2011-12
期刊：
影响因子：
6.7
通讯作者：
Dimopoulos G
中科院分区：
文献类型：
--
作者：
Dong Y;Das S;Cirimotich C;Souza-Neto JA;McLean KJ;Dimopoulos G
恶性疟原虫是人类疟疾的一种病原体，由按蚊传播。疟疾寄生虫在其孢子生殖发育期间受到蚊子先天免疫系统的强烈攻击。我们已经使用基因工程来创建免疫增强的斯氏按蚊蚊子，通过在中肠和脂肪体组织中编码IMD通路控制的NF-κ B Rel 2转录因子的转基因的血餐诱导表达。转基因蚊子对疟原虫和微生物感染表现出更大的抵抗力，这是由于涉及多个效应器的及时协调的组织特异性免疫攻击。在实验室条件下，这种基因修饰对蚊子适应性的影响相对较弱，这鼓励进一步研究这种疟疾控制方法。疟疾是由按蚊传播的疟原虫寄生虫引起的，蚊子的先天免疫系统在几个孢子生殖阶段阻断寄生虫方面起着重要作用。我们以前的研究表明，主要的蚊子免疫途径之一，IMD，是重要的防御对人类疟疾寄生虫在三个主要的疟疾媒介，冈比亚按蚊，A。stephensi和A. albimanus。转录因子Rel 2受IMD途径调节，并控制几种有效的抗疟原虫免疫因子的表达。在这项研究中，我们已经使用生殖系转化技术，以产生转基因按蚊斯氏按蚊与血餐诱导表达Rel 2转录在中肠和脂肪体组织。这些转基因蚊子对人类疟疾寄生虫几乎完全具有抵抗力，这是因为抗疟原虫效应基因及时协调组织特异性表达的结果。在实验室条件下，这种遗传修饰的健身成本是最小的，这表明该系统可以用于疟疾控制策略的发展。
A causative agent of human malaria, Plasmodium falciparum, is transmitted by Anopheles mosquitoes. The malaria parasite is under intensive attack from the mosquito's innate immune system during its sporogonic development. We have used genetic engineering to create immune-enhanced Anopheles stephensi mosquitoes through blood meal-inducible expression of a transgene encoding the IMD pathway-controlled NF-kB Rel2 transcription factor in the midgut and fat-body tissue. Transgenic mosquitoes showed greater resistance to Plasmodium and microbial infection as a result of timely concerted tissue-specific immune attacks involving multiple effectors. The relatively weak impact of this genetic modification on mosquito fitness under laboratory conditions encourages further investigation of this approach for malaria control. Malaria is caused by the Plasmodium parasites which are transmitted by the Anopheles mosquitoes, and the mosquito's innate immune system plays an important role in blocking the parasite at several sporogonic stages. Our previous studies have shown that one of the major mosquito immune pathways, IMD, is important in the defense against the human malaria parasite in three major malaria vectors, Anopheles gambiae, A. stephensi, and A. albimanus. The transcription factor Rel2 is regulated by the IMD pathway and controls the expression of several potent anti-Plasmodium immune factors. In this study, we have used germ-line transformation technology to generate transgenic Anopheles stephensi mosquitoes with blood meal-inducible expression of Rel2 transcripts in both midgut and fat-body tissues. These transgenic mosquitoes were close to completely resistant to human malaria parasites as a result of the timely concerted tissue-specific expression of anti-Plasmodium effector genes. Under laboratory conditions, the fitness cost of this genetic modification was minimal, suggesting that this system could be utilized for the development of a malaria control strategy.
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