Host 5-HT affectsPlasmodiumtransmission in mosquitoes via modulating mosquito mitochondrial homeostasis

Abstract

SUMMARYMalaria parasites hijack the metabolism of their mammalian host during the blood-stage cycle.Anophelesmosquitoes depend on mammalian blood to survive and to transmit malaria parasites. However, it remains understudied whether changes in host metabolism affect parasite transmission in mosquitoes. In this study, we discovered thatPlasmodiuminfection 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 toAnopheles stephensienhanced its resistance toPlasmodium bergheiinfection 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.