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Impact of Reactive Oxygen Species produced by their sand fly vector on Leishmania sexual hybrid formation

Objective

By transmitting hundreds of pathogens causing important human mortality and morbidity, vector insects are a major public health threat. Even if intrinsic insect parameters such as immune response are known to impact their vectorial capacities, the vector/pathogen interaction is still little understood. Phlebotomine sand flies are responsible for the transmission of Leishmania parasites, causing Leishmaniasis. This disease produces a wide spectrum of symptoms, due to a high genetic diversity of parasite strains. In addition to their clonal reproduction, Leishmania can engage in a cryptic sexual cycle resulting in hybrid progeny. Sexual mating is believed to be a major source of Leishmania genetic diversity, which drives changes in tissue tropism, pathology and drug resistance. Experimental generation of hybrids, until recently confined to parasites growing in the sand fly gut, is now possible to achieve in vitro. However, despite the possibility to culture high quantities of parasites, the frequency of hybrids generated in vivo is much higher than in vitro, showing that the vector gut environment is particularly adapted for Leishmania sexual mating. The mechanisms of Leishmania sexual reproduction and the parameters rendering the vector’s gut favorable to this process are currently unknown. I recently observed that pre-exposing parental parasite cultures to Reactive Oxygen Species (ROS) leads to an increased hybrid production in vitro, which led me to hypothesize that ROS, present in large amount in the sand fly gut, could be one of these parameters. Using a dual genetic approach applied on both the parasite and the vector, I aim to decipher the impact of the ROS produced by the sand fly gut cells on the engagement of Leishmania parasites in a sexual reproduction path. This project will generate important knowledge on the Leishmania/sand fly interaction and will set the stage for my future independent research group on the subject.

Coordinator

INSTITUT PASTEUR
Net EU contribution
€ 211 754,88
Address
Rue Du Docteur Roux 25-28
75724 Paris Cedex 15
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Non-EU contribution
No data