YOUR RESOURCES ARE MY RESOURCES: PARASITE MIGRATION AND THE HOST FIBRINOLYTIC SYSTEM IN FASCIOLOSIS (ULISES)
Call: State Programme for R&D&I Oriented to the Challenges of Society 2018 (Type JIN)
Referencia: RTI2018-093463-J-I00
Funding entities: Ministry of Science, Innovation and Universities (MCIU), State Research Agency (AEI) and European Regional Development Fund (ERDF).
Duration: 2019 – 2022
Principal Investigator: Javier González Miguel (IRNASA-CSIC).
Participating researchers: Fernando Simón Martín (University of Salamanca) and Aniceto Méndez Sánchez (University of Córdoba).
IRNASA Participants: David Becerro Recio and María González Sánchez.
Summary
The ULISES project focuses on the parasite Fasciola hepatica, whose infection, fasciolosis, causes serious problems in the world’s livestock population by infecting different species of herbivorous mammals. In addition, humans co-inhabiting at-risk areas may also be affected. Definitive hosts become infected after ingesting resistance forms attached to aquatic plants, and once in the gut, the juvenile stages of the parasite pass through the gut and begin a complex migration route to the bile ducts. This migratory ability is shared by a large number of parasites, which through these strategies are able to evade the immune response of the host until they reach their adult stages.
Therefore, the knowledge of how these mechanisms develop can provide us with tools to block the biological cycles of parasites before they reach their final locations.
In previous works we have discovered the ability of different parasites to interact with the fibrinolytic system of the host, being able to “hijack” the final protein of this pathway, plasmin, and use it for their own benefit. Plasmin is able to degrade a large number of components, including extracellular matrices, so it has been postulated that this mechanism could be used by parasites to migrate through the tissues of their hosts.
The main objective of the project is to demonstrate that the juvenile stages of Fasciola hepatica use host plasmin to migrate from the intestine to their final location in the bile ducts. This will be done using a novel in vitro model in which the juvenile stages of the parasite and the host intestinal epithelium cells will be studied together. Once the first conclusions have been drawn, the real participation of this mechanism in parasite migration will be demonstrated in an in vivo model of mice deficient in plasmin.
The results of the project will make it possible to identify interesting targets in the future, not only in fasciolosis, but also in other parasitosis, whose blocking could interrupt the biological cycles of the parasites before they develop their adult stages and, therefore, before the most serious infections become established in their hosts.
