Human IGF1 extends lifespan and enhances resistance to Plasmodium falciparum infection in the malaria vector Anopheles stephensi
Human IGF1 extends lifespan and enhances resistance to Plasmodium falciparum infection in the malaria vector Anopheles stephensi
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DOI：
10.1242/jeb.078873
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发表时间：
2013-01-01
影响因子：
2.8
通讯作者：
Luckhart, Shirley
中科院分区：
文献类型：
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作者：
Drexler, Anna;Nuss, Andrew;Luckhart, Shirley
高度保守的胰岛素/胰岛素样生长因子 (IGF) 信号传导 (IIS) 通路调节多种生物体的代谢、发育、寿命和免疫。先前的研究表明，摄入血粉中的人胰岛素可以激活蚊子的 IIS，导致寿命缩短并增加疟原虫感染。由于人类 IGF1 在血液中的浓度高于胰岛素，并且与寿命和免疫过程在功能上相关，因此我们预测，摄入血粉中的人类 IGF1 会影响史氏按蚊的寿命和疟疾寄生虫感染。在这里，我们证明，摄入的 IGF1 的生理水平（如胰岛素）可以在充满血液的中肠中完整保留长达 30 小时，并传播到蚊子体内，并且这两种肽都会激活蚊子细胞和中肠中的 IIS。在相同水平下，与对照组相比，单独摄入 IGF1 的蚊子平均寿命延长了 23%，更重要的是，与对照组相比，当摄入受感染的血粉时，感染恶性疟原虫的蚊子的患病率降低了 20% 以上，寄生虫数量降低了 35-50%。因此，摄入IGF1对蚊子寿命和免疫力的影响与摄入胰岛素相反。这些结果提供了第一个证据，证明昆虫细胞可以在功能上区分哺乳动物胰岛素和 IGF1。此外，鉴于之前通过基因靶向 IIS 来改变蚊子寿命和疟疾寄生虫传播的成功，这项研究表明，对血液中 IIS 激活配体的更全面了解可用于优化疟疾控制的转基因策略。
The highly conserved insulin/insulin-like growth factor (IGF) signaling (IIS) pathway regulates metabolism, development, lifespan and immunity across a wide range of organisms. Previous studies have shown that human insulin ingested in the blood meal can activate mosquito IIS, resulting in attenuated lifespan and increased malaria parasite infection. Because human IGF1 is present at higher concentrations in blood than insulin and is functionally linked with lifespan and immune processes, we predicted that human IGF1 ingested in a blood meal would affect lifespan and malaria parasite infection in the mosquito Anopheles stephensi. Here we demonstrate that physiological levels of ingested IGF1, like insulin, can persist intact in the blood-filled midgut for up to 30 h and disseminate into the mosquito body, and that both peptides activate IIS in mosquito cells and midgut. At these same levels, ingested IGF1 alone extended average mosquito lifespan by 23% compared with controls and, more significantly, when ingested in infected blood meals, reduced the prevalence of Plasmodium falciparum-infected mosquitoes by >20% and parasite load by 35-50% compared with controls. Thus, the effects of ingested IGF1 on mosquito lifespan and immunity are opposite to those of ingested insulin. These results offer the first evidence that insect cells can functionally discriminate between mammalian insulin and IGF1. Further, in light of previous success in genetically targeting IIS to alter mosquito lifespan and malaria parasite transmission, this study indicates that a more complete understanding of the IIS-activating ligands in blood can be used to optimize transgenic strategies for malaria control.