Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses
Abstract Fasciola hepatica, a global worm parasite of humans and their livestock, regulates host innate immune responses within hours of infection. Host macrophages, essential to the first-line defence mechanisms, are quickly restricted in their ability to initiate a classic protective pro-inflammat...
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Nature Portfolio
2021
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oai:doaj.org-article:c491f3abaaee4078b8355327c7eadde92021-12-02T14:02:53ZFasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses10.1038/s41598-021-86125-12045-2322https://doaj.org/article/c491f3abaaee4078b8355327c7eadde92021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86125-1https://doaj.org/toc/2045-2322Abstract Fasciola hepatica, a global worm parasite of humans and their livestock, regulates host innate immune responses within hours of infection. 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, fhe-miR-125b, is released by the parasite via exosomes and is homologous to a mammalian miRNA, hsa-miR-125b, that is known to regulate the activation of pro-inflammatory M1 macrophages. We show that the parasite fhe-miR-125b loads onto the mammalian Argonaut protein (Ago-2) within macrophages during infection and, therefore, propose that it mimics host miR-125b 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.Nham TranAlison RicafrenteJoyce ToMaria LundTania M. MarquesMargarida Gama-CarvalhoKrystyna CwiklinskiJohn P. DaltonSheila DonnellyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
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Medicine R Science Q Nham Tran Alison Ricafrente Joyce To Maria Lund Tania M. Marques Margarida Gama-Carvalho Krystyna Cwiklinski John P. Dalton Sheila Donnelly Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses |
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Abstract Fasciola hepatica, a global worm parasite of humans and their livestock, regulates host innate immune responses within hours of infection. 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, fhe-miR-125b, is released by the parasite via exosomes and is homologous to a mammalian miRNA, hsa-miR-125b, that is known to regulate the activation of pro-inflammatory M1 macrophages. We show that the parasite fhe-miR-125b loads onto the mammalian Argonaut protein (Ago-2) within macrophages during infection and, therefore, propose that it mimics host miR-125b 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. |
format |
article |
author |
Nham Tran Alison Ricafrente Joyce To Maria Lund Tania M. Marques Margarida Gama-Carvalho Krystyna Cwiklinski John P. Dalton Sheila Donnelly |
author_facet |
Nham Tran Alison Ricafrente Joyce To Maria Lund Tania M. Marques Margarida Gama-Carvalho Krystyna Cwiklinski John P. Dalton Sheila Donnelly |
author_sort |
Nham Tran |
title |
Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses |
title_short |
Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses |
title_full |
Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses |
title_fullStr |
Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses |
title_full_unstemmed |
Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses |
title_sort |
fasciola hepatica hijacks host macrophage mirna machinery to modulate early innate immune responses |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/c491f3abaaee4078b8355327c7eadde9 |
work_keys_str_mv |
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