Increased insulin signaling in the Anopheles stephensi fat body regulates metabolism and enhances the host response to both bacterial challenge and Plasmodium falciparum infection.

Increased insulin signaling in the Anopheles stephensi fat body regulates metabolism and enhances the host response to both bacterial challenge and Plasmodium falciparum infection.
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史氏按蚊脂肪体中胰岛素信号的增加可调节新陈代谢并增强宿主对细菌挑战和恶性疟原虫感染的反应。

DOI:
10.1016/j.ibmb.2021.103669
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发表时间:
2021-12
影响因子:
3.8
通讯作者:
Riehle MA
Riehle MA
中科院分区:
农林科学2区
文献类型:
--
作者:
Hun LV;Cheung KW;Brooks E;Zudekoff R;Luckhart S;Riehle MA

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在脊椎动物和无脊椎动物中,胰岛素/胰岛素样生长因子1 (IGF1)信号(IIS)级联是高度保守的,在许多不同的生理过程中起着至关重要的作用。在蚊子体内对IIS有反应的许多组织中,脂肪体在新陈代谢、寿命、繁殖和先天免疫中起着核心作用。我们之前已经证明,在成年斯氏按蚊和埃及伊蚊中,脂肪体特异性表达的活性Akt (IIS关键信号分子)激活了IIS级联并延长了寿命。此外,我们发现转基因雌性蚊子比非转基因蚊子产生更多的卵黄蛋白原(Vg)蛋白,尽管这并没有转化为更高的繁殖力。这些结果促使我们进一步研究IIS如何影响这些转基因蚊子的免疫、代谢、生长和发育。我们观察到,在3-5 d龄的转基因蚊子中,糖原、海藻糖、甘油三酯、葡萄糖和蛋白质的含量与非转基因的同类蚊子相比发生了显著变化,而在18 d龄的转基因蚊子中,只有甘油三酯发生了显著变化。更重要的是,我们证明了增强的脂肪体IIS降低了转基因果蝇中恶性疟原虫感染的患病率和强度。stephensi。此外,挑战转基因安。与非转基因对照相比,革兰氏阳性菌和革兰氏阴性菌感染的斯氏杆菌改变了几种抗菌肽(AMPs)和两种抗疟原虫基因——一氧化氮合酶(NOS)和硫酯补体样蛋白(TEP1)的表达。成年雌安鱼脂肪体IIS升高。与非转基因对照相比,斯氏杆菌对转基因蚊子的体型、生长或后代发育几乎没有影响。这项研究证实并扩展了我们对胰岛素信号在调节蚊子脂肪体多种功能中的关键作用的理解。
In vertebrates and invertebrates, the insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) cascade is highly conserved and plays a vital role in many different physiological processes. Among the many tissues that respond to IIS in mosquitoes, the fat body has a central role in metabolism, lifespan, reproduction, and innate immunity. We previously demonstrated that fat body specific expression of active Akt, a key IIS signaling molecule, in adult Anopheles stephensi and Aedes aegypti activated the IIS cascade and extended lifespan. Additionally, we found that transgenic females produced more vitellogenin (Vg) protein than non-transgenic mosquitoes, although this did not translate into increased fecundity. These results prompted us to further examine how IIS impacts immunity, metabolism, growth and development of these transgenic mosquitoes. We observed significant changes in glycogen, trehalose, triglycerides, glucose, and protein in young (3–5 d) transgenic mosquitoes relative to non-transgenic sibling controls, while only triglycerides were significantly changed in older (18 d) transgenic mosquitoes. More importantly, we demonstrated that enhanced fat body IIS decreased both the prevalence and intensity of Plasmodium falciparum infection in transgenic An. stephensi. Additionally, challenging transgenic An. stephensi with Gram-positive and Gram-negative bacteria altered the expression of several antimicrobial peptides (AMPs) and two anti-Plasmodium genes, nitric oxide synthase (NOS) and thioester complement-like protein (TEP1), relative to non-transgenic controls. Increased IIS in the fat body of adult female An. stephensi had little to no impact on body size, growth or development of progeny from transgenic mosquitoes relative to non-transgenic controls. This study both confirms and expands our understanding of the critical roles insulin signaling plays in regulating the diverse functions of the mosquito fat body.
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发表时间: 2013-01-01
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