BACKGROUND: Leishmaniasis 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. METHODS: Phlebotomus 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). RESULTS: Aza 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. CONCLUSIONS: These results highlight the critical role of ecdysone in regulating the development and immunity of P. perniciosus, which potentially could interfere with Leishmania infection.

• Klíčová slova
• Phlebotomus perniciosus, Antimicrobial peptides, Azadirachtin, Ecdysone,
• MeSH
• antimikrobiální peptidy genetika   farmakologie   MeSH
• ekdyson * MeSH
• hmyz - vektory účinky léků   genetika   parazitologie   imunologie   MeSH
• hmyzí proteiny genetika   metabolismus   MeSH
• larva * účinky léků   imunologie   genetika   MeSH
• limoniny * farmakologie   MeSH
• Phlebotomus * účinky léků   genetika   parazitologie   imunologie   MeSH
• shazování tělního pokryvu účinky léků   MeSH
• signální transdukce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antimikrobiální peptidy MeSH
• azadirachtin MeSH Prohlížeč
• ekdyson * MeSH
• hmyzí proteiny MeSH
• limoniny * MeSH

The rapid spread of highly aggressive arboviruses, parasites, and bacteria along with the development of resistance in the pathogens and parasites, as well as in their arthropod vectors, represents a huge challenge in modern parasitology and tropical medicine. Eco-friendly vector control programs are crucial to fight, besides malaria, the spread of dengue, West Nile, chikungunya, and Zika virus, as well as other arboviruses such as St. Louis encephalitis and Japanese encephalitis. However, research efforts on the control of mosquito vectors are experiencing a serious lack of eco-friendly and highly effective pesticides, as well as the limited success of most biocontrol tools currently applied. Most importantly, a cooperative interface between the two disciplines is still lacking. To face this challenge, we have reviewed a wide number of promising results in the field of green-fabricated pesticides tested against mosquito vectors, outlining several examples of synergy with classic biological control tools. The non-target effects of green-fabricated nanopesticides, including acute toxicity, genotoxicity, and impact on behavioral traits of mosquito predators, have been critically discussed. In the final section, we have identified several key challenges at the interface between "green" nanotechnology and classic biological control, which deserve further research attention.

• Klíčová slova
• Arbovirus, Biosafety, Dengue, Genotoxicity, Japanese encephalitis, Malaria, Nanosynthesis, West Nile virus, Zika virus,
• MeSH
• dengue MeSH
• hmyz - vektory účinky léků   MeSH
• infekce virem zika mikrobiologie   MeSH
• lidé MeSH
• malárie MeSH
• moskyti - kontrola * metody   MeSH
• One Health MeSH
• virus zika MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH