近日，国际著名杂志《美国国家科学院院刊》PNAS在线刊登了美国加利福尼亚大学研究人员的最新研究成果“Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti，”，文章中，作者解释了沃尔巴克氏体细菌通过激活活性氧依赖的Toll途径来控制伊蚊体内的登革热病毒。
登革热是一种病毒引起的疾病，主要发生在热带，全球每年大约有5000万人受感染。登革热爆发的严重性在增强，涉及的地理范围也在扩大。能传染登革热的蚊子对能杀死它们的杀虫剂也逐渐变得有抗药性。登革热通常不会致人死亡，但是它能让患者病重。对于发展中国家人民来说这能造成严重的经济后果。
沃尔巴克式体存活于细胞的细胞质中，通过母体排卵的方式一代代的繁衍。它造成细胞质不相容，给细菌提供一种强大的机制侵入昆虫群体。受感染的母体既可以和受感染的雄性也可以和没有受感染的雄性交配，但是未受感染的雌性只能和未受感染的雄性成功交配。如果未受感染的雌性和受感染的雄性交配，它的后代会死亡。这意味着受感染的雌性具有选择上的优势，因为它们在选择雄性时有更大的选择范围。
文章中，作者阐述了沃尔巴克式体细菌是如何对登革热病毒产生抗性进而影响伊蚊的，作者用沃尔巴克式体感染伊蚊后，进行了微阵列实验，发现伊蚊体内与免疫和氧化还原反应相关的基因的转录表达量都升高了，细菌的感染可以诱导文字体内的氧化应激性以及活性氧水平的升高，活性氧的水平和Toll途径的激活直接相关，而Toll途径直接介导抗氧化剂的表达用来应对氧化压力，这种免疫途径对抗微生物多肽（如防御素类或者蛾血素）的激活也是极其相关的，作者目前的证据显示，抗微生物多肽在含沃尔巴克式体的蚊子中可以抑制登革热病毒的繁殖，目前利用转基因蚊子和RNAi的方法可以达到同样的目的，就是在含沃尔巴克式体的蚊子中可以抑制登革热病毒的增殖。
研究者进行了一系列的实验，最后发现了共生细菌可以利用宿主的免疫系统来促进自己在宿主内的持续感染，最终在有登革热病毒的蚊子体内持续生存，最终使带有病毒的蚊子死亡，遏制登革热病毒的传播，作者的研究发现将会给抑制蚊子疾病的传播带来非常大的帮助和支持。（生物谷Bioon.com）
（T.Shen编译 如有问题请及时指正）
doi:10.1073/pnas.1116932108
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Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti
Xiaoling Pana, Guoli Zhoua, Jiahong Wua,b, Guowu Biana,c, Peng Lua, Alexander S. Raikheld,e,1, and Zhiyong Xia,c,1
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.
