MicroRNA-regulation of Anopheles gambiae immunity to Plasmodium falciparum infection and midgut microbiota.
MicroRNA-regulation of Anopheles gambiae immunity to Plasmodium falciparum infection and midgut microbiota.
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DOI：
10.1016/j.dci.2014.10.016
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发表时间：
2015-03
影响因子：
2.9
通讯作者：
Dimopoulos, George
中科院分区：
文献类型：
--
作者：
Dennison, Nathan J.;BenMarzouk-Hidalgo, Omar J.;Dimopoulos, George
疟原虫对疟疾媒介冈比亚按蚊中肠的入侵触发了介导抗寄生虫防御的免疫基因的转录变化。这种反应主要由Toll和免疫缺陷（IMD）途径调节。以确定是否一个。冈比亚微小RNA（miRNAs）参与调节抗疟原虫防御，我们表明抑制miRNAs生物合成导致对恶性疟原虫感染的抗性增加。An.的计算机模拟分析冈比亚免疫效应基因鉴定了具有miRNA结合位点的多个转录物。恶性疟原虫感染和未感染蚊子中肠组织的比较miRNA微阵列丰度分析显示，在感染的中肠中，miRNA aga-miR-989和aga-miR-305的丰度升高。aga-miR-305的拮抗剂抑制增加了对恶性疟原虫感染的抗性并抑制了中肠微生物群。相反，用人工aga-miR-305模拟物处理蚊子增加了对恶性疟原虫感染的易感性，并导致中肠微生物群的扩增，表明aga-miR-305通过负调节蚊子免疫应答而充当恶性疟原虫和肠道微生物群激动剂。aga-miR-305靶基因的计算机预测鉴定了几种抗疟原虫效应物。我们的研究表明，安。gambiae aga-miR-305可能通过免疫效应基因的转录后修饰来调节抗疟原虫应答和中肠微生物群。
Invasion of the malaria vector Anopheles gambiae midgut by Plasmodium parasites triggers transcriptional changes of immune genes that mediate the antiparasitic defense. This response is largely regulated by the Toll and Immune deficiency (IMD) pathways. To determine whether An. gambiae microRNAs (miRNAs) are involved in regulating the anti-Plasmodium defense, we showed that suppression of miRNA biogenesis results in increased resistance to Plasmodium falciparum infection. In silico analysis of An. gambiae immune effector genes identified multiple transcripts with miRNA binding sites. A comparative miRNA microarray abundance analysis of P. falciparum infected and naïve mosquito midgut tissues showed elevated abundance of miRNAs aga-miR-989 and aga-miR-305 in infected midguts. Antagomir inhibition of aga-miR-305 increased resistance to P. falciparum infection and suppressed the midgut microbiota. Conversely, treatment of mosquitoes with an artificial aga-miR-305 mimic increased susceptibility to P. falciparum infection and resulted in expansion of midgut microbiota, suggesting that aga-miR-305 acts as a P. falciparum and gut microbiota agonist by negatively regulating the mosquito immune response. In silico prediction of aga-miR-305 target genes identified several anti-Plasmodium effectors. Our study shows that An. gambiae aga-miR-305 regulates the anti-Plasmodium response and midgut microbiota, likely through post-transcriptional modification of immune effector genes.
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影响因子：
6.7
作者：
Dong Y;Aguilar R;Xi Z;Warr E;Mongin E;Dimopoulos G
通讯作者：
Dimopoulos G
影响因子：
5.3
作者：
Clayton AM;Dong Y;Dimopoulos G
通讯作者：
Dimopoulos G
影响因子：
6.7
作者：
Garver LS;Bahia AC;Das S;Souza-Neto JA;Shiao J;Dong Y;Dimopoulos G
通讯作者：
Dimopoulos G
影响因子：
2.6
作者：
Campbell CL;Harrison T;Hess AM;Ebel GD
通讯作者：
Ebel GD
影响因子：
2.9
作者：
Fullaondo, Ane;Lee, So Young
通讯作者：
Lee, So Young