近日,，來自約翰霍普金斯大學的研究者首次發(fā)現(xiàn)蚊子機體的蛋白可以轉(zhuǎn)換功能來抵御寄生蟲的感染，相關研究成果刊登在了近日的國際雜志PLoS Pathogens上,。
研究者這項最新研究建立在前期研究的基礎之上,，這項最新研究中，他們發(fā)現(xiàn)在岡比亞按蚊中,，沉默Caspar回路的一個基因可以激活lmd途徑的轉(zhuǎn)錄因子Rel2的表達,。Rel2的激活可以開啟TEP1、APL1和FBN9的效應,，從而殺死蚊子機體腸道內(nèi)的瘧原蟲,。更為重要的是，這項研究發(fā)現(xiàn)了lmd途徑信號轉(zhuǎn)導因子和效應因子會在動合子早期階段降低寄生蟲的感染,。
識別并理解各個關鍵角色的作用對于控制lmd途徑來抵御寄生蟲的感染至關重要,。
研究者George表示，目前他們已經(jīng)可以通過遺傳改造產(chǎn)生對瘧疾有抗性的蚊子,。研究者使用一種RNA干擾的方法來講lmd途徑中的基因敲除,，當途徑組分失活后，研究者就可以觀察到蚊子對寄生蟲感染抗性的變化情況,。每年在全世界范圍內(nèi)瘧疾可以導致80萬人死亡,，其中死亡者大多數(shù)為小孩。
最后研究者表示,，我們可以對蚊子免疫系統(tǒng)的各個組分進行操作修飾,，以便可以識別出殺死瘧疾寄生蟲的有效成分。（生物谷Bioon.com）
編譯自：Immune System 'Circuitry' That Kills Malaria in Mosquitoes Identified
編譯者：天使托
doi:10.1371/journal.ppat.1002737
PMC:
PMID:
Anopheles Imd Pathway Factors and Effectors in Infection Intensity-Dependent Anti-Plasmodium Action
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.
