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During <jats:italic>F<\/jats:italic>. <jats:italic>hepatica<\/jats:italic> 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 <jats:italic>F<\/jats:italic>. <jats:italic>hepatica<\/jats:italic> 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/Principal Findings<\/jats:title>\n<jats:p>A tegument-enriched antigenic extract of FhNEJ (FhNEJ-Teg) was obtained <jats:italic>in vitro<\/jats:italic>, and its capability to bind the zymogen plasminogen (PLG) and enhance its conversion to the active protease, plasmin, were analyzed by a combination of enzyme-linked immunosorbent, chromogenic and immunofluorescence assays. Additionally, PLG-binding proteins in FhNEJ-Teg were identified by bidimensional electrophoresis coupled to mass spectrometry analysis, and the interactions were validated using FhNEJ recombinant proteins.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions\/Significance<\/jats:title>\n<jats:p>Our results show that FhNEJ-Teg contains proteins that bind PLG and stimulate its activation to plasmin, which could facilitate the traversal of the intestinal wall by FhNEJ and contribute to the successful establishment of the parasite within its mammalian host. Altogether, our findings contribute to a better understanding of host-parasite relationships during early fasciolosis and may be exploited from a pharmacological and\/or immunological perspective for the development of treatment and control strategies against this global disease.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0010936","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T17:56:54Z","timestamp":1682099814000},"page":"e0010936","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Fasciola hepatica juveniles interact with the host fibrinolytic system as a potential early-stage invasion mechanism"],"prefix":"10.1371","volume":"17","author":[{"given":"Judit","family":"Serrat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Becerro-Recio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Torres-Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Sim\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Adela","family":"Valero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Bargues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Mas-Coma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Siles-Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4279-4761","authenticated-orcid":true,"given":"Javier","family":"Gonz\u00e1lez-Miguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"pntd.0010936.ref001","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-3-030-18616-6_4","volume-title":"Digenetic Trematodes","author":"S Mas\u2013Coma","year":"2019"},{"key":"pntd.0010936.ref002","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.rvsc.2020.10.011","article-title":"Fascioliasis and fasciolopsiasis: current knowledge and future trends","volume":"134","author":"M Siles\u2013Lucas","year":"2021","journal-title":"Res Vet Sci"},{"issue":"5","key":"pntd.0010936.ref003","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.4269\/ajtmh.18-0372","article-title":"Socioeconomic factors associated with Fasciola hepatica infection among children from 26 communities of the Cusco region of Peru","volume":"99","author":"CM Webb","year":"2018","journal-title":"Am J Trop Med"},{"issue":"3","key":"pntd.0010936.ref004","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.3390\/ijerph19031120","article-title":"One Health action against human fascioliasis in the Bolivian altiplano: food, water, housing, behavioural traditions, social aspects, and livestock management linked to disease transmission and infection sources","volume":"19","author":"R Angles","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"pntd.0010936.ref005","unstructured":"World Health Organization (2021). 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