The role of NF-kappaB factor REL2 in the Aedes aegypti immune response.
The role of NF-kappaB factor REL2 in the Aedes aegypti immune response.
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DOI：
10.1016/j.ibmb.2009.01.007
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发表时间：
2009-04
影响因子：
3.8
通讯作者：
Raikhel, Alexander S.
中科院分区：
文献类型：
--
作者：
Antonova, Yevgeniya;Alvarez, Kanwal S.;Kim, Yu Jung;Kokoza, Vladimir;Raikhel, Alexander S.
蚊子传播许多疾病，这些疾病继续对世界各地的公共卫生造成巨大负担。转基因蚊子不受病媒传播的病原体的影响，与病媒控制以及药物和疫苗开发相结合，构成了预计在未来击败蚊子传播疾病的手段武器库。蚊子转基因可以对其主要免疫途径进行组织特异性操作，并增强研究蚊子与病原体相互作用的能力。在这里，我们报告了两个独立的埃及伊蚊转基因株的产生，高表达核因子-κB转录因子REL2，它是果蝇调味品的同源物，被证明是在蚊子脂肪体内的卵黄蛋白原启动子的控制下。我们发现，这种REL2在脂肪体中的过度表达导致防御素A、C和D以及天蚕素A和N的转录激活，以及防御素A蛋白的翻译和分泌到血淋巴中。我们还证明，REL2的诱导导致蚊子对被测试的革兰氏阴性和革兰氏阳性细菌的抵抗力增加。重要的是，转基因REL2的诱导可显著降低Ae的易感性。埃及伊蚊对鸡疟原虫的感染。一直以来，野生型蚊子中REL2的RNAi敲除导致感染反应中防御素A和抗菌素A的表达延迟，并增加了对细菌和鸡疫霉菌的易感性。此外，我们的转基因分析表明，蚊子REL2的N-末端，包括富含His/Gln和富含丝氨酸的区域，在其反式激活特性中发挥了作用。
Mosquitoes transmit numerous diseases that continue to be an enormous burden on public health worldwide. Transgenic mosquitoes impervious to vector-borne pathogens, in concert with vector control and drug and vaccine development, comprise an arsenal of means anticipated to defeat mosquito-spread diseases in the future. Mosquito transgenesis allows tissue-specific manipulation of their major immune pathways and enhances the ability to study mosquito–pathogen interactions. Here, we report the generation of two independent transgenic strains of Aedes aegypti overexpressing the NF-κB transcriptional factor REL2, a homologue of Drosophila Relish, which is shown to be under the control of the vitellogenin promoter in the mosquito fat body after a blood meal. We show that this REL2 overexpression in the fat body results in transcriptional activation of Defensins A, C, and D, and Cecropins A and N, as well as translation and secretion of Defensin A protein into the hemolymph. We also demonstrate that induction of REL2 results in the increased resistance of the mosquito to tested Gram-negative and Gram-positive bacteria. Importantly, induction of transgenic REL2 leads to the significant decrease in susceptibility of Ae. aegypti to Plasmodium gallinaceum infection. Consistently, RNAi knockdown of REL2 in wild-type mosquitoes results in a delay in Defensin A and Cecropin A expression in response to infection and in increased susceptibility to both bacteria and P. gallinaceum. Moreover, our transgenic assays demonstrate that the N-terminus of the mosquito REL2, which includes the His/Gln-rich and Serine-rich regions, plays a role in its transactivation properties.
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