Chloroquine mediated modulation of Anopheles gambiae gene expression.
Chloroquine mediated modulation of Anopheles gambiae gene expression.
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氯喹介导的冈比亚基因表达的调节。
DOI：
10.1371/journal.pone.0002587
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发表时间：
2008-07-02
期刊：
影响因子：
3.7
通讯作者：
Silveira, Henrique
中科院分区：
文献类型：
--
作者：
Abrantes, Patricia;Dimopoulos, George;Grosso, Ana Rita;do Rosario, Virgilio E.;Silveira, Henrique
蚊子体内疟原虫的发育对疟疾传播至关重要，并取决于寄生虫与各种细胞类型和对感染有积极和消极影响的特定蚊子因素的相互作用。虽然蚊子的防御反应有助于在这些阶段减少寄生虫数量，但已知血粉的某些成分有利于感染，从而增加了传播的风险。在蚊子的血粉中存在抗疟疾药物氯喹与疟原虫对蚊子的感染性增加有关，这可能是由于氯喹干扰蚊子抵御感染的能力所致。在这项研究中，我们报告了一个详细的调查冈比亚按蚊基因的差异调节氯喹的存在下，血粉，使用A。冈比亚cDNA微阵列。氯喹对转录本丰度的影响分别评价了未感染和伯氏疟原虫感染的蚊子。氯喹被发现会影响转录本的丰度，这些转录本编码参与各种过程的蛋白质，包括免疫、凋亡、细胞骨架和对氧化应激的反应。这种差异基因表达的模式可以解释减弱的蚊子防御反应，这是在氯喹处理的蚊子中观察到的感染性增加的原因。本研究的结果表明，氯喹可以干扰几个假定的蚊子防御疟原虫的基因表达水平的机制，并强调需要更好地了解抗疟药对寄生虫传播的影响。
Plasmodium development in the mosquito is crucial for malaria transmission and depends on the parasite's interaction with a variety of cell types and specific mosquito factors that have both positive and negative effects on infection. Whereas the defensive response of the mosquito contributes to a decrease in parasite numbers during these stages, some components of the blood meal are known to favor infection, potentiating the risk of increased transmission. The presence of the antimalarial drug chloroquine in the mosquito's blood meal has been associated with an increase in Plasmodium infectivity for the mosquito, which is possibly caused by chloroquine interfering with the capacity of the mosquito to defend against the infection. In this study, we report a detailed survey of the Anopheles gambiae genes that are differentially regulated by the presence of chloroquine in the blood meal, using an A. gambiae cDNA microarray. The effect of chloroquine on transcript abundance was evaluated separately for non-infected and Plasmodium berghei-infected mosquitoes. Chloroquine was found to affect the abundance of transcripts that encode proteins involved in a variety of processes, including immunity, apoptosis, cytoskeleton and the response to oxidative stress. This pattern of differential gene expression may explain the weakened mosquito defense response which accounts for the increased infectivity observed in chloroquine-treated mosquitoes. The results of the present study suggest that chloroquine can interfere with several putative mosquito mechanisms of defense against Plasmodium at the level of gene expression and highlight the need for a better understanding of the impacts of antimalarial agents on parasite transmission.
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