Molecular Characterization of the Interplay between Fasciola hepatica Juveniles and Laminin as a Mechanism to Adhere to and Break through the Host Intestinal Wall
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Published:2023-05-03
Issue:9
Volume:24
Page:8165
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Serrat Judit1,
Torres-Valle María1,
López-García Marta1ORCID,
Becerro-Recio David1,
Siles-Lucas Mar1,
González-Miguel Javier1ORCID
Affiliation:
1. Laboratory of Helminth Parasites of Zoonotic Importance (ATENEA), Institute of Natural Resources and Agrobiology of Salamanca (IRNASA-CSIC), C/Cordel de Merinas 40-52, 37008 Salamanca, Spain
Abstract
Fasciola hepatica is the main causative agent of fasciolosis, a zoonotic parasitic disease of growing public health concern. F. hepatica metacercariae are ingested by the host and excyst in the intestine, thereby releasing the newly excysted juveniles (FhNEJ), which traverse the gut wall and migrate towards the biliary ducts. Since blocking F. hepatica development is challenging after crossing of the intestinal wall, targeting this first step of migration might result in increased therapeutic success. The intestinal extracellular matrix (ECM) is constituted by a network of structural proteins, including laminin (LM) and fibronectin (FN), that provide mechanical support while acting as physical barrier against intestinal pathogens. Here, we employed ELISA and immunofluorescent assays to test for the presence of LM- and FN-binding proteins on a tegument-enriched antigenic fraction of FhNEJ, and further determined their identity by two-dimensional electrophoresis coupled to mass spectrometry. Additionally, we performed enzymatic assays that revealed for the first time the capability of the juvenile-specific cathepsin L3 to degrade LM, and that LM degradation by FhNEJ proteins is further potentiated in the presence of host plasminogen. Finally, a proteomic analysis showed that the interaction with LM triggers protein changes in FhNEJ that may be relevant for parasite growth and adaptation inside the mammalian host. Altogether, our study provides valuable insights into the molecular interplay between FhNEJ and the intestinal ECM, which may lead to the identification of targetable candidates for the development of more effective control strategies against fasciolosis.
Funder
Ministerio de Ciencia
Junta de Castilla y León
European Regional Development Fund
Spanish Ministry of Science and Innovation
Ministerio de Ciencia e Innovación
Instituto de Salud Carlos III
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis