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腾讯登录PLoS Patho：研究者发现蚊子杀灭体内疟原虫的分子机制
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近日，来自约翰霍普金斯大学的研究者首次发现蚊子机体的蛋白可以转换功能来抵御寄生虫的感染，相关研究成果刊登在了近日的国际杂志<em>PLoS Pathogens</em>上。
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研究者这项最新研究建立在前期研究的基础之上，这项最新研究中，他们发现在冈比亚按蚊中，沉默Caspar回路的一个基因可以激活lmd途径的转录因子Rel2的表达。Rel2的激活可以开启TEP1、APL1和FBN9的效应，从而杀死蚊子机体肠道内的疟原虫。更为重要的是，这项研究发现了lmd途径信号转导因子和效应因子会在动合子早期阶段降低寄生虫的感染。
识别并理解各个关键角色的作用对于控制lmd途径来抵御寄生虫的感染至关重要。
研究者George表示，目前他们已经可以通过遗传改造产生对疟疾有抗性的蚊子。研究者使用一种RNA干扰的方法来讲lmd途径中的基因敲除，当途径组分失活后，研究者就可以观察到蚊子对寄生虫感染抗性的变化情况。每年在全世界范围内疟疾可以导致80万人死亡，其中死亡者大多数为小孩。
最后研究者表示，我们可以对蚊子免疫系统的各个组分进行操作修饰，以便可以识别出杀死疟疾寄生虫的有效成分。
<img src="http://www.bioon.com/biology/UploadFiles/201206/2012060916213499.jpg" alt="" width="113" height="149" border="0" />
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<a title="" href="http://dx.doi.org/doi:10.1371/journal.ppat.1002737" target="_blank">doi:10.1371/journal.ppat.1002737</a>
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<br/><strong>Anopheles Imd Pathway Factors and Effectors in Infection Intensity-Dependent Anti-Plasmodium Action</strong><br/>
Lindsey S. Garver¤a, Ana C. Bahia, Suchismita Das, Jayme A. Souza-Neto¤b, Jessica Shiao, Yuemei Dong, George Dimopoulos*
The Anopheles gambiae immune response against Plasmodium falciparum, an etiological agent of human malaria, has been identified as a source of potential anti-Plasmodium genes and mechanisms to be exploited in efforts to control the malaria transmission cycle. One such mechanism is the Imd pathway, a conserved immune signaling pathway that has potent anti-P. falciparum activity. Silencing the expression of caspar, a negative regulator of the Imd pathway, or over-expressing rel2, an Imd pathway-controlled NFkappaB transcription factor, confers a resistant phenotype on A. gambiae mosquitoes that involves an array of immune effector genes. However, unexplored features of this powerful mechanism that may be essential for the implementation of a malaria control strategy still remain. Using RNA interference to singly or dually silence caspar and other components of the Imd pathway, we have identified genes participating in the anti-Plasmodium signaling module regulated by Caspar, each of which represents a potential target to achieve over-activation of the pathway. We also determined that the Imd pathway is most potent against the parasite's ookinete stage, yet also has reasonable activity against early oocysts and lesser activity against late oocysts. We further demonstrated that caspar silencing alone is sufficient to induce a robust anti-P. falciparum response even in the relative absence of resident gut microbiota. Finally, we established the relevance of the Imd pathway components and regulated effectors TEP1, APL1, and LRIM1 in parasite infection intensity-dependent defense, thereby shedding light on the relevance of laboratory versus natural infection intensity models. Our results highlight the physiological considerations that are integral to a thoughtful implementation of Imd pathway manipulation in A. gambiae as part of an effort to limit the malaria transmission cycle, and they reveal a variety of previously unrecognized nuances in the Imd-directed immune response against P. falciparum.
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<div id="ztload"> </div>
近日，来自约翰霍普金斯大学的研究者首次发现蚊子机体的蛋白可以转换功能来抵御寄生虫的感染，相关研究成果刊登在了近日的国际杂志<em>PLoS Pathogens</em>上。
<!--more-->
研究者这项最新研究建立在前期研究的基础之上，这项最新研究中，他们发现在冈比亚按蚊中，沉默Caspar回路的一个基因可以激活lmd途径的转录因子Rel2的表达。Rel2的激活可以开启TEP1、APL1和FBN9的效应，从而杀死蚊子机体肠道内的疟原虫。更为重要的是，这项研究发现了lmd途径信号转导因子和效应因子会在动合子早期阶段降低寄生虫的感染。
识别并理解各个关键角色的作用对于控制lmd途径来抵御寄生虫的感染至关重要。
研究者George表示，目前他们已经可以通过遗传改造产生对疟疾有抗性的蚊子。研究者使用一种RNA干扰的方法来讲lmd途径中的基因敲除，当途径组分失活后，研究者就可以观察到蚊子对寄生虫感染抗性的变化情况。每年在全世界范围内疟疾可以导致80万人死亡，其中死亡者大多数为小孩。
最后研究者表示，我们可以对蚊子免疫系统的各个组分进行操作修饰，以便可以识别出杀死疟疾寄生虫的有效成分。
<img src="http://www.bioon.com/biology/UploadFiles/201206/2012060916213499.jpg" alt="" width="113" height="149" border="0" />
<div id="ztload">
<div>
<div>
<a title="" href="http://dx.doi.org/doi:10.1371/journal.ppat.1002737" target="_blank">doi:10.1371/journal.ppat.1002737</a>
PMC:
PMID:
</div>
<div>
<br/><strong>Anopheles Imd Pathway Factors and Effectors in Infection Intensity-Dependent Anti-Plasmodium Action</strong><br/>
Lindsey S. Garver¤a, Ana C. Bahia, Suchismita Das, Jayme A. Souza-Neto¤b, Jessica Shiao, Yuemei Dong, George Dimopoulos*
The Anopheles gambiae immune response against Plasmodium falciparum, an etiological agent of human malaria, has been identified as a source of potential anti-Plasmodium genes and mechanisms to be exploited in efforts to control the malaria transmission cycle. One such mechanism is the Imd pathway, a conserved immune signaling pathway that has potent anti-P. falciparum activity. Silencing the expression of caspar, a negative regulator of the Imd pathway, or over-expressing rel2, an Imd pathway-controlled NFkappaB transcription factor, confers a resistant phenotype on A. gambiae mosquitoes that involves an array of immune effector genes. However, unexplored features of this powerful mechanism that may be essential for the implementation of a malaria control strategy still remain. Using RNA interference to singly or dually silence caspar and other components of the Imd pathway, we have identified genes participating in the anti-Plasmodium signaling module regulated by Caspar, each of which represents a potential target to achieve over-activation of the pathway. We also determined that the Imd pathway is most potent against the parasite's ookinete stage, yet also has reasonable activity against early oocysts and lesser activity against late oocysts. We further demonstrated that caspar silencing alone is sufficient to induce a robust anti-P. falciparum response even in the relative absence of resident gut microbiota. Finally, we established the relevance of the Imd pathway components and regulated effectors TEP1, APL1, and LRIM1 in parasite infection intensity-dependent defense, thereby shedding light on the relevance of laboratory versus natural infection intensity models. Our results highlight the physiological considerations that are integral to a thoughtful implementation of Imd pathway manipulation in A. gambiae as part of an effort to limit the malaria transmission cycle, and they reveal a variety of previously unrecognized nuances in the Imd-directed immune response against P. falciparum.
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