Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti
Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti
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DOI：
10.1073/pnas.1116932108
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发表时间：
2012-01-03
影响因子：
11.1
通讯作者：
Xi, Zhiyong
中科院分区：
文献类型：
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作者：
Pan, Xiaoling;Zhou, Guoli;Xi, Zhiyong
沃尔巴克氏体是一种母体传播的共生细菌，由于其独特的操纵宿主繁殖的能力，可以在昆虫种群中传播。当引入非本地蚊子宿主时，沃尔巴克氏体诱导对许多人类病原体的抗性，包括登革热病毒（DENV）、疟原虫和丝状线虫，但所涉及的分子机制尚不清楚。在这项研究中，我们已经破译了沃尔巴克氏体感染如何影响埃及伊蚊宿主诱导对DENV的抗性。微阵列分析表明，与免疫和还原氧化反应相关的基因转录本在Ae中上调。感染沃尔巴克氏体的埃及伊蚊。这种细菌的感染导致其蚊子宿主氧化应激和活性氧水平的增加。活性氧的升高与Toll通路的激活有关，而Toll通路在调节抗氧化剂的表达以抵消氧化应激中是必不可少的。这种免疫途径也负责激活抗菌肽-防御素和抗菌肽。我们提供的证据表明，这些抗菌肽参与抑制DENV在沃尔巴克氏体感染的蚊子增殖。转基因Ae的利用。RNAi耗竭方法在证明防御素和抗菌素在沃尔巴克氏体感染的伊蚊耐药性中的作用方面发挥了重要作用。埃及伊蚊到DENV。这些结果表明，一种共生细菌可以操纵宿主防御系统，以促进其自身的持续感染，从而降低蚊子宿主人类病原体的能力。我们的发现将有助于制定蚊子传播疾病的控制策略。
Wolbachia are maternally transmitted symbiotic bacteria that can spread within insect populations because of their unique ability to manipulate host reproduction. When introduced to nonnative mosquito hosts, Wolbachia induce resistance to a number of human pathogens, including dengue virus (DENV), Plasmodium, and filarial nematodes, but the molecular mechanism involved is unclear. In this study, we have deciphered how Wolbachia infection affects the Aedes aegypti host in inducing resistance to DENV. The microarray assay indicates that transcripts of genes with functions related to immunity and reduction-oxidation (redox) reactions are up-regulated in Ae. aegypti infected with Wolbachia. Infection with this bacterium leads to induction of oxidative stress and an increased level of reactive oxygen species in its mosquito host. Reactive oxygen species elevation is linked to the activation of the Toll pathway, which is essential in mediating the expression of antioxidants to counterbalance oxidative stress. This immune pathway also is responsible for activation of antimicrobial peptides-defensins and cecropins. We provide evidence that these antimicrobial peptides are involved in inhibition of DENV proliferation in Wolbachia-infected mosquitoes. Utilization of transgenic Ae. aegypti and the RNAi depletion approach has been instrumental in proving the role of defensins and cecropins in the resistance of Wolbachia-infected Ae. aegypti to DENV. These results indicate that a symbiotic bacterium can manipulate the host defense system to facilitate its own persistent infection, resulting in a compromise of the mosquito's ability to host human pathogens. Our discoveries will aid in the development of control strategies for mosquito-transmitted diseases.