Transcriptional mediators Kto and Skd are involved in the regulation of the IMD pathway and anti-Plasmodium defense in Anopheles gambiae.
Transcriptional mediators Kto and Skd are involved in the regulation of the IMD pathway and anti-Plasmodium defense in Anopheles gambiae.
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DOI：
10.1371/journal.pone.0045580
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dimopoulos G
中科院分区：
文献类型：
--
作者：
Chen Y;Dong Y;Sandiford S;Dimopoulos G
疟疾寄生虫疟原虫必须在其按蚊宿主（疟原虫的主要载体）中完成复杂的生命周期。蚊子通过参与NF-κB免疫信号通路IMD抵抗人类恶性疟原虫的感染。在这里，我们表明，保守的转录介质Kto和Skd参与蚊子IMD途径的调节。在冈比亚按蚊细胞系L5-3中，RNAi介导的Kto和Skd的消耗导致Cec 1的转录丰度降低，这是由IMD途径控制的。沉默这两个基因也导致蚊子对细菌和恶性疟原虫感染的易感性增加，但对啮齿动物疟疾寄生虫伯氏疟原虫的感染没有影响。我们还表明，Kto和Skd不是Rel 2或IMD途径的其他关键因子的转录共激活因子;然而，它们参与IMD途径的调节，这对于蚊子防御恶性疟原虫至关重要。
The malarial parasite Plasmodium must complete a complex lifecycle in its Anopheles mosquito host, the main vector for Plasmodium. The mosquito resists infection with the human malarial parasite P. falciparum by engaging the NF-κB immune signaling pathway, IMD. Here we show that the conserved transcriptional mediators Kto and Skd are involved in the regulation of the mosquito IMD pathway. RNAi-mediated depletion of Kto and Skd in the Anopheles gambiae cell line L5-3 resulted in a decrease in the transcript abundance of Cec1, which is controlled by the IMD pathway. Silencing the two genes also resulted in an increased susceptibility of the mosquito to bacterial and Plasmodium falciparum infection, but not to infection with the rodent malaria parasite P. berghei. We also showed that Kto and Skd are not transcriptional co-activators of Rel2 or other key factors of the IMD pathway; however, they participate in the regulation of the IMD pathway, which is crucial for the mosquito’s defense against P. falciparum.
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