Fasciola hepatica juveniles interact with the host fibrinolytic system as a potential early-stage invasion mechanism

22 páginas, 8 figuras
The trematode Fasciola hepatica is the most widespread causative agent of fasciolosis, a parasitic disease that mainly affects humans and ruminants worldwide. During F. hepatica infection, newly excysted juveniles (FhNEJ) emerge in the duodenum of the mammalian host and migrate towards their definitive location, the intra-hepatic biliary ducts. Understanding how F. hepatica traverses the intestinal wall and migrates towards the liver is pivotal for the development of more successful strategies against fasciolosis. The central enzyme of the mammalian fibrinolytic system is plasmin, a serine protease whose functions are exploited by a number of parasite species owing to its broad spectrum of substrates, including components of tissue extracellular matrices. The aim of the present work is to understand whether FhNEJ co-opt the functions of their host fibrinolytic system as a mechanism to facilitate trans-intestinal migration.
This work was supported by the JIN project ‘ULYSSES’ (RTI2018-093463-J-100 to J.G.M.) funded by the Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, UE). IRNASA-CSIC group acknowledges funding received from Project “CLU-2019-05 - IRNASA-CSIC Unit of Excellence”, funded by the Junta de Castilla y León cofunded by the European Union (FEDER “Europe drives our growth”) and funding from the Programme for strengthening research structures "Stairway to excellence" internationalisation aid, cofunded by the Junta de Castilla y León and the European Regional Development Fund. M.S.L.acknowledges the financial support of the Spanish Ministry of Science and Innovation (Project PID2019-108782RB-C22). J.S. and D.B.R. acknowledge the support of the Junta de Castilla y León for their Predoctoral contracts. J.G.M. is supported by the ‘Ramón y Cajal’ program (RYC2020-030575-I) of the Ministerio de Ciencia e Innovación. Valencia centre collaboration funded by: CIBER-Consorcio Centro de Investigación Biomédica en Red- (CB21/13/00056), Instituto de Salud Carlos III, Ministry of Science and Innovation and European Union – NextGenerationEU; the Red de Investigación de Centros de Enfermedades Tropicales - RICET (RD16/0027/0023) of the PN de I+D+I, ISCIII-Subdirección General de Redes y Centros de Investigación Cooperativa RETICS, Ministry of Health and Consumption, Madrid; the PROMETEO Program, Programa de Ayudas para Grupos de Investigación de Excelencia (2021/004), Generalitat Valenciana, Valencia, Spain. The proteomics laboratory where LC-MS/MS analysis was performed is a member of Proteored, PRB3 and is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by the Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript