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Neuroendocrine regulation of Phlebotomus perniciosus immunity and microbiota: fighting Leishmania infection

Objective

Vector-borne diseases create considerable risks to human health. Leishmaniases are a group of neglected vector-borne diseases caused by protists parasites from the Leishmania genus. Approximately 350 million people around the world are at risk of being infected with Leishmania, and clinical manifestations in humans vary from cutaneous to visceral types. Leishmania is transmitted to humans by hematophagous female sand flies (Diptera, Psychodidae, Phlebotominae). Here we focus on Phlebotomus perniciosus, the natural vector of Leishmania infantum (the causative agent of visceral leishmaniasis) in the western region of the Mediterranean basin Europe. Leishmania cycle occurs in the sand fly midgut, where parasites must overcome natural barriers such as high activity levels of midgut digestive proteases, the competition with the native gut microbiota, and the activation of sand fly immune responses. Recently it was shown that insect immunity is under hormonal regulation; ecdysone hormone binds to its receptor (EcR) and triggers the expression of IMD immune signalling pathway-related genes. In sand flies gut, the IMD pathway controls Leishmania infection, but ecdysone's role in sand fly immunity and microbiota has never been studied. The NEPHIMLEI project, in a pioneering way, proposes manipulating P. perniciosus neuroendocrine system to affect sand fly gut immunity and microbiota intending the blockage of L. infantum development in the vector. Sand fly ecdysone function will be impaired by azadirachtin (an ecdysone inhibitor) oral treatment or silencing the EcR gene by RNAi. Also, sand fly immunity will be enhanced by suppressing repressor genes from both ecdysone and IMD pathways (Eip75B and caspar, respectively) using the CRISPR/Cas9 system. The altered ecdysone signalling could change P. perniciosus IMD-related immune responses, affecting microbiota and inducing sand fly resistance against L. infantum.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2021-PF-01

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Coordinator

UNIVERZITA KARLOVA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 166 278,72
Address
OVOCNY TRH 560/5
116 36 Praha 1
Czechia

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Region
Česko Praha Hlavní město Praha
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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