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Host macrophages, essential to the first-line defence mechanisms, are quickly restricted in their ability to initiate a classic protective pro-inflammatory immune response. We found that macrophages from infected animals are enriched with parasite-derived micro(mi)RNAs. The most abundant of these miRNAs, <jats:italic>fhe-miR-125b<\/jats:italic>, is released by the parasite via exosomes and is homologous to a mammalian miRNA, <jats:italic>hsa-miR-125b<\/jats:italic>, that is known to regulate the activation of pro-inflammatory M1 macrophages. We show that the parasite <jats:italic>fhe-miR-125b<\/jats:italic> loads onto the mammalian Argonaut protein (Ago-2) within macrophages during infection and, therefore, propose that it mimics host <jats:italic>miR-125b<\/jats:italic> to negatively regulate the production of inflammatory cytokines. The hijacking of the miRNA machinery controlling innate cell function could be a fundamental mechanism by which worm parasites disarm the early immune responses of their host to ensure successful infection.<\/jats:p>","DOI":"10.1038\/s41598-021-86125-1","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T11:04:07Z","timestamp":1616583847000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses"],"prefix":"10.1038","volume":"11","author":[{"given":"Nham","family":"Tran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Ricafrente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"To","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Lund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania M.","family":"Marques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarida","family":"Gama-Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystyna","family":"Cwiklinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Dalton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Donnelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"86125_CR1","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/j.0105-2896.2004.00191.x","volume":"201","author":"RM Maizels","year":"2004","unstructured":"Maizels, R. 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