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Azadirachtin disrupts ecdysone signaling and alters sand fly immunity

dc.contributor.authorStahl Vieira, Cecilia
dc.contributor.authorBisogno, Sara
dc.contributor.authorSalvemini, Marco
dc.contributor.authorLoza Telleria, Erich
dc.contributor.authorVolf, Petr
dc.date.accessioned2025-03-07T15:11:00Z
dc.date.available2025-03-07T15:11:00Z
dc.date.issued2024
dc.identifier.urihttps://hdl.handle.net/20.500.14178/3031
dc.description.abstractBackgroundLeishmaniasis is a group of neglected vector-borne diseases transmitted by phlebotomine sand flies. Leishmania parasites must overcome various defenses in the sand fly midgut, including the insects's immune response. Insect immunity is regulated by the ecdysone hormone, which binds to its nuclear receptor (EcR) and activates the transcription of genes involved in insect immunity. However, the role of ecdysone in sand fly immunity has never been studied. Phlebotomus perniciosus is a natural vector of Leishmania infantum; here, we manipulated its neuroendocrine system using azadirachtin (Aza), a natural compound known to affect ecdysone synthesis.MethodsPhlebotomus perniciosus larvae and adult females were fed on food containing either Aza alone or Aza plus ecdysone, and the effects on mortality and ecdysis were evaluated. Genes related to ecdysone signaling and immunity were identified in P. perniciosus, and the expression of antimicrobial peptides (AMPs), EcR, the ecdysone-induced genes Eip74EF and Eip75B, and the transcription factor serpent were analyzed using quantitative polymerase chain reaction (PCR).ResultsAza treatment inhibited molting of first-instar (L1) larvae to L2, with only 10% of larvae molting compared to 95% in the control group. Serpent and Eip74EF, attacin, defensin 1, and defensin 2 genes were downregulated by Aza treatment in larvae. Similarly, Aza-treated adult females also presented suppression of ecdysone signaling-related genes and the AMPs attacin and defensin 2. Notably, all gene repression caused by Aza was reversed by adding ecdysone concomitantly with Aza to the larval or female food, indicating that these genes are effective markers for ecdysone repression.ConclusionsThese results highlight the critical role of ecdysone in regulating the development and immunity of P. perniciosus, which potentially could interfere with Leishmania infection.en
dc.language.isoen
dc.relation.urlhttps://doi.org/10.1186/s13071-024-06589-8
dc.rightsCreative Commons Uveďte původ 4.0 Internationalcs
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.titleAzadirachtin disrupts ecdysone signaling and alters sand fly immunityen
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/legalcode
dc.date.updated2025-03-07T15:11:00Z
dc.subject.keyword<italic>Phlebotomus perniciosus</italic>en
dc.subject.keywordAzadirachtinen
dc.subject.keywordEcdysoneen
dc.subject.keywordAntimicrobial peptidesen
dc.subject.keyworden
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM/OP VVV/CZ.02.1.01/0.0/0.0/16_019/0000759
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/UK/COOP/COOP
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/EU/FP9/NEPHIMLEI
dc.date.embargoStartDate2025-03-07
dc.type.obd73
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1186/s13071-024-06589-8
dc.identifier.utWos001381577800001
dc.identifier.eidScopus2-s2.0-85212692256
dc.identifier.obd659638
dc.identifier.pubmed39707409
dc.subject.rivPrimary10000::10600
dcterms.isPartOf.nameParasites & Vectors
dcterms.isPartOf.issn1756-3305
dcterms.isPartOf.journalYear2024
dcterms.isPartOf.journalVolume17
dcterms.isPartOf.journalIssue1
uk.faculty.primaryId115
uk.faculty.primaryNamePřírodovědecká fakultacs
uk.faculty.primaryNameFaculty of Scienceen
uk.department.primaryId1038
uk.department.primaryNameKatedra parazitologiecs
uk.department.primaryNameDepartment of Parasitologyen
dc.type.obdHierarchyCsČLÁNEK V ČASOPISU::článek v časopisu::původní článekcs
dc.type.obdHierarchyEnJOURNAL ARTICLE::journal article::original articleen
dc.type.obdHierarchyCode73::152::206en
uk.displayTitleAzadirachtin disrupts ecdysone signaling and alters sand fly immunityen


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