Host 5-HT affects Plasmodium transmission in mosquitoes via modulating mosquito mitochondrial homeostasis.

IF 5.5 1区医学 Q1 MICROBIOLOGY

PLoS Pathogens Pub Date : 2024-10-15 eCollection Date: 2024-10-01 DOI:10.1371/journal.ppat.1012638

Li Gao, Benguang Zhang, Yuebiao Feng, Wenxu Yang, Shibo Zhang, Jingwen Wang

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Abstract

Malaria parasites hijack the metabolism of their mammalian host during the blood-stage cycle. Anopheles mosquitoes depend on mammalian blood to lay eggs and to transmit malaria parasites. However, it remains understudied whether changes in host metabolism affect parasite transmission in mosquitoes. In this study, we discovered that Plasmodium infection significantly decreased the levels of the tryptophan metabolite, 5-hydroxytryptamine (5-HT), in both humans and mice. The reduction led to the decrease of 5-HT in mosquitoes. Oral supplementation of 5-HT to Anopheles stephensi enhanced its resistance to Plasmodium berghei infection by promoting the generation of mitochondrial reactive oxygen species. This effect was due to the accumulation of dysfunctional mitochondria caused by 5-HT-mediated inhibition of mitophagy. Elevating 5-HT levels in mouse serum significantly suppressed parasite infection in mosquitoes. In summary, our data highlight the critical role of metabolites in animal blood in determining the capacity of mosquitoes to control parasite infection.

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宿主5-羟色胺通过调节蚊子线粒体的平衡影响疟原虫在蚊子中的传播。

疟疾寄生虫在血液阶段周期中劫持了哺乳动物宿主的新陈代谢。按蚊依赖哺乳动物的血液产卵并传播疟疾寄生虫。然而，宿主新陈代谢的变化是否会影响寄生虫在蚊子体内的传播，这方面的研究仍然不足。在这项研究中，我们发现疟原虫感染会显著降低人类和小鼠体内色氨酸代谢物--5-羟色胺（5-HT）的水平。这种降低导致蚊子体内的 5-HT 减少。通过促进线粒体活性氧的生成，给按蚊口服 5-HT 可增强其对疟原虫感染的抵抗力。这种效应是由于 5-HT 介导的线粒体吞噬抑制作用导致功能失调的线粒体积累所致。提高小鼠血清中的 5-HT 水平可显著抑制蚊子的寄生虫感染。总之，我们的数据强调了动物血液中的代谢物在决定蚊子控制寄生虫感染能力方面的关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PLoS Pathogens MICROBIOLOGY-PARASITOLOGY

自引率

3.00%

发文量

598

期刊介绍： Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.