Abstract
Sand flies, present in all intertropical regions, are dipteran insects belonging to the Psychodidae family and the Phlebotominae subfamily. About a hundred species have been identified as vectors, of which 40% are proven vectors. These species are involved in the transmission of several pathogens such as Leishmania and Phlebovirus. Leishmania are Kinetoplastidae protozoa of the Trypanosomatidae family belonging to the genus Leishmania responsible for parasitic diseases. They infect a wide range of vertebrate hosts, including humans. For example, Leishmania infantum is a species that circulates in the Mediterranean region and can cause severe visceral forms if left untreated. Viruses of the genus Phlebovirus belong to the Phenuiviridae family and the Bunyavirales order. Some Phlebovirus are associated with human diseases, such as Toscana virus (TOSV) with a neurotropic activity. The parasite Le. infantum and TOSV co-circulate in the Mediterranean basin and share some vector species, such as Phlebotomus perniciosus. Studies have shown co-infections in mammalian hosts, but none have been able to confirm this in sand fly natural populations. The biological interactions between TOSV and sand flies and between these two pathogens in host and vector are still poorly understood.In this context, the main objective of this thesis project is to study, through an experimental approach, the interactions of these two pathogens with their vector to better understand the impact on their transmission and on the sand fly biology. This thesis has been divided into three chapters. The first chapter deals with the sand fly model, the establishment and maintenance of the colony in our laboratory, and the development of experimental infections. The second chapter studies the interactions between the parasite Le. infantum and the vector Ph. perniciosus. These experiments show the infection impact on one of the sand fly life history traits: infected females lay significantly more eggs. The third chapter explores the natural cycle of TOSV in Ph. perniciosus. The study of infection dynamics in Ph. perniciosus reveals that, depending on the TOSV dose ingested by the vector, systemic infection occurs between three and five days. In addition, TOSV infection resulted in an increase of egg hatching time. Therefore, the results clearly demonstrate that both pathogens have an impact on the biology of the vector and the conditions of infection can have consequences on their transmission.This thesis provides fundamental knowledge on the biology of vector-pathogen interactions in the sand fly-Phlebovirus-Leishmania model. The results represent a solid and essential baseline for the study of Ph. perniciosus co-infection by these two pathogens. Looking ahead, the study of their interactions within the vector will allow to determine whether the presence of one can modulate the infectious potential of the other and its transmission to the host.