Rapamycin inhibits pathogen transmission in mosquitoes by promoting immune activation.
Rapamycin inhibits pathogen transmission in mosquitoes by promoting immune activation.
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雷帕霉素通过促进免疫激活抑制病原体在蚊子中的传播。
DOI：
10.1371/journal.ppat.1009353
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发表时间：
2021-03
期刊：
影响因子：
6.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Feng Y;Chen L;Gao L;Dong L;Wen H;Song X;Luo F;Cheng G;Wang J
反复进食血液为蚊卵发育和病原体传播提供了必要的营养物质。雷帕霉素的靶点，TOR途径，是卵黄发生所必需的。然而，其对病原体传播的影响仍有待阐明。在这里，我们展示了雷帕霉素，一种TOR途径的抑制剂，有效地抑制了斯氏按蚊中伯氏疟原虫的感染。一种。注射雷帕霉素或喂食雷帕霉素处理的小鼠的斯氏杆菌对伯氏肺孢子虫感染的抵抗力增强。暴露出一种。雷帕霉素涂层表面的斯氏杆菌不仅减少了卵囊和子孢子的数量，而且还损害了蚊子的存活和繁殖力。转录组分析表明，雷帕霉素对寄生虫感染的抑制作用是通过增强免疫应答，特别是免疫途径和补体系统的调节因子NF-κB转录因子REL2实现的。在雷帕霉素处理的蚊子中，REL2的敲除取消了补体样蛋白TEP1和SPCLIP1的诱导，并消除了雷帕霉素介导的对疟原虫感染的耐受性。总之，这些发现证明了TOR途径在调节蚊子免疫反应中的关键作用，从而影响媒介能力。自生蚊子必须吃脊椎动物的血粉才能完成卵子发生。反复吸血使蚊子成为传播疾病的有效媒介。被摄取的血液激活的TOR途径被认为是蚊子卵黄形成的重要调节因子。在此，我们证明蛋白激酶TOR参与了蚊子对疟原虫感染的易感性的调节。雷帕霉素抑制TOR通路可上调REL2的表达，REL2是一种控制多种免疫效应分子表达的转录因子。增强的免疫反应反过来又促进了寄生虫的清除。因此，TOR途径不仅在调节蚊子繁殖方面发挥着双重作用，而且在它们的媒介潜力中也发挥着双重作用。
Repeated blood meals provide essential nutrients for mosquito egg development and routes for pathogen transmission. The target of rapamycin, the TOR pathway, is essential for vitellogenesis. However, its influence on pathogen transmission remains to be elucidated. Here, we show that rapamycin, an inhibitor of the TOR pathway, effectively suppresses Plasmodium berghei infection in Anopheles stephensi. An. stephensi injected with rapamycin or feeding on rapamycin-treated mice showed increased resistance to P. berghei infection. Exposing An. stephensi to a rapamycin-coated surface not only decreased the numbers of both oocysts and sporozoites but also impaired mosquito survival and fecundity. Transcriptome analysis revealed that the inhibitory effect of rapamycin on parasite infection was through the enhanced activation of immune responses, especially the NF-κB transcription factor REL2, a regulator of the immune pathway and complement system. Knockdown of REL2 in rapamycin-treated mosquitoes abrogated the induction of the complement-like proteins TEP1 and SPCLIP1 and abolished rapamycin-mediated refractoriness to Plasmodium infection. Together, these findings demonstrate a key role of the TOR pathway in regulating mosquito immune responses, thereby influencing vector competence. Anautogenous mosquitoes must consume vertebrate blood meals to complete oogenesis. Repeated blood feeding makes the mosquitoes efficient disease-transmitting vectors. The TOR pathway activated by ingested blood is known as an important regulator for vitellogenesis in mosquitoes. Herein, we show that the protein kinase TOR is involved in the regulation of mosquitoes’ susceptibility to Plasmodium infection. Inhibition of the TOR pathway by rapamycin upregulates the expression of REL2, a transcription factor controlling the expression of a variety of immune effectors. The enhanced immune responses in turn promote parasite elimination. Therefore, the TOR pathway plays a dual role in not only regulating mosquito reproduction but also in their vector potential.
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卵巢的雌激素激素独立于黄热病蚊子中的胰岛素受体，埃及埃及。
影响因子：
3.8
作者：
Dhara A;Eum JH;Robertson A;Gulia-Nuss M;Vogel KJ;Clark KD;Graf R;Brown MR;Strand MR
通讯作者：
Strand MR
影响因子：
6.4
作者：
Gordon EB;Hart GT;Tran TM;Waisberg M;Akkaya M;Skinner J;Zinöcker S;Pena M;Yazew T;Qi CF;Miller LH;Pierce SK
通讯作者：
Pierce SK
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：
2.4
作者：
FOWLER, RE;BILLINGSLEY, PF;SINDEN, RE
通讯作者：
SINDEN, RE