{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T18:47:43Z","timestamp":1792349263391,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012638","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T00:00:00Z","timestamp":1728950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1902211"],"award-info":[{"award-number":["U1902211"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Pilot Program for Basic Research - Fudan University","award":["22TQ015"],"award-info":[{"award-number":["22TQ015"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Malaria parasites hijack the metabolism of their mammalian host during the blood-stage cycle. <jats:italic>Anopheles<\/jats:italic> 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 <jats:italic>Plasmodium<\/jats:italic> 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 <jats:italic>Anopheles stephensi<\/jats:italic> enhanced its resistance to <jats:italic>Plasmodium berghei<\/jats:italic> 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.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012638","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T17:33:01Z","timestamp":1729013581000},"page":"e1012638","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Host 5-HT affects Plasmodium transmission in mosquitoes via modulating mosquito mitochondrial homeostasis"],"prefix":"10.1371","volume":"20","author":[{"given":"Li","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benguang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuebiao","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6794-2604","authenticated-orcid":true,"given":"Jingwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,15]]},"reference":[{"key":"ppat.1012638.ref001","volume-title":"World Malaria Report 2022.","author":"WHO","year":"2022"},{"issue":"6906","key":"ppat.1012638.ref002","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature01097","article-title":"Genome sequence of the human malaria parasite Plasmodium falciparum","volume":"419","author":"MJ Gardner","year":"2002","journal-title":"Nature"},{"issue":"7","key":"ppat.1012638.ref003","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/s42255-021-00404-9","article-title":"Metabolome modulation of the host adaptive immunity in human malaria","volume":"3","author":"W Abdrabou","year":"2021","journal-title":"Nat Metab"},{"issue":"11","key":"ppat.1012638.ref004","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1093\/infdis\/jiy727","article-title":"Identifying the Components of Acidosis in Patients With Severe Plasmodium falciparum Malaria Using Metabolomics","volume":"219","author":"SJ Leopold","year":"2019","journal-title":"The Journal of infectious diseases"},{"issue":"11","key":"ppat.1012638.ref005","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1084\/jem.20070819","article-title":"Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria","volume":"204","author":"TW Yeo","year":"2007","journal-title":"J Exp Med"},{"issue":"4","key":"ppat.1012638.ref006","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1086\/590209","article-title":"Recovery of endothelial function in severe falciparum malaria: relationship with improvement in plasma L-arginine and blood lactate concentrations","volume":"198","author":"TW Yeo","year":"2008","journal-title":"The Journal of infectious diseases"},{"issue":"3","key":"ppat.1012638.ref007","doi-asserted-by":"crossref","first-page":"e1004667","DOI":"10.1371\/journal.ppat.1004667","article-title":"Impaired systemic tetrahydrobiopterin bioavailability and increased dihydrobiopterin in adult falciparum malaria: association with disease severity, impaired microvascular function and increased endothelial activation.","volume":"11","author":"TW Yeo","year":"2015","journal-title":"PLoS pathogens."},{"issue":"8","key":"ppat.1012638.ref008","doi-asserted-by":"crossref","first-page":"5249","DOI":"10.1128\/IAI.73.8.5249-5251.2005","article-title":"Prolonged survival of a murine model of cerebral malaria by kynurenine pathway inhibition","volume":"73","author":"CJ Clark","year":"2005","journal-title":"Infection and immunity"},{"issue":"431","key":"ppat.1012638.ref009","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aan6007","article-title":"Malaria in pregnancy alters l-arginine bioavailability and placental vascular development","volume":"10","author":"CR McDonald","year":"2018","journal-title":"Science translational medicine"},{"issue":"3","key":"ppat.1012638.ref010","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/BF00929173","article-title":"Pathology of Anopheles stephensi after infection with Plasmodium berghei berghei. 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