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The liver exerted a Th2 immune response at very early stages after the primoinfection with <jats:italic>F. hepatica<\/jats:italic> that induced the downregulation of IFN-\u03b3, followed by a Th1\/Th2\/Treg response although the late stages were characterised by the expression of Th1\/Th2 immune mediators. Contrarily, in reinfected sheep a robust mixed Th1\/Th2\/Treg immune response was found at very early stages meanwhile at late stages we observed a Th2\/Treg immune response overcoming the expression of Th1 immune mediators. However, the HLN displayed a completely different Th1\/Th2\/Treg expression profile compared to the liver. Primoinfections with <jats:italic>F. hepatica<\/jats:italic> in HLN induced a mixed Th1\/Th2\/Treg environment from early stages, establishing a Th2 immune response at a late stage. However, the reinfected sheep exerted a Th2 immune response at early stages led by the IL-4 expression in opposition to the Th1\/Th2\/Treg found in the liver, meanwhile at late stages the HLN of reinfected sheep exerted a mixed Th1\/Th2\/Treg immune response. This is the first work publishing the expression of immune mediators in the liver and HLN from reinfected sheep with <jats:italic>F. hepatica.<\/jats:italic> The study of the immune responses exerted by the natural host in the target organs directly implied in the development of <jats:italic>F. hepatica<\/jats:italic> are crucial to better understand the immunopathogenesis of the fasciolosis being a key factor to develop effective vaccines.<\/jats:p>","DOI":"10.1186\/s13567-022-01129-7","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T16:03:34Z","timestamp":1673366614000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Fasciola hepatica primoinfections and reinfections in sheep drive distinct Th1\/Th2\/Treg immune responses in liver and hepatic lymph node at early and late stages"],"prefix":"10.1186","volume":"54","author":[{"given":"Mar\u00eda Teresa","family":"Ruiz-Campillo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Mar\u00eda","family":"Barrero-Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nieves","family":"Abril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Zafra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro","family":"Buffoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Mart\u00ednez-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Javier","family":"Mart\u00ednez-Moreno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8850-7388","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Molina-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"1129_CR1","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.micpath.2017.06.006","volume":"109","author":"K Mehmood","year":"2017","unstructured":"Mehmood K, Zhang H, Sabir AJ, Abbas RZ, Ijaz M, Durrani AZ, Saleem MH, Ur Rehman M, Iqbal MK, Wang Y, Ahmad HI, Abbas T, Hussain R, Ghori MT, Ali S, Khan AU, Li J (2017) A review on epidemiology, global prevalence and economical losses of fasciolosis in ruminants. 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