Host 5-HT Affects Plasmodium Transmission in Mosquitoes Via Modulating Mosquito Mitochondrial Homeostasis

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2024 Oct 15

PMID 39405338

Authors

Li Gao

Benguang Zhang

Yuebiao Feng

Wenxu Yang

Shibo Zhang

Jingwen Wang

Affiliations

Soon will be listed here.

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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