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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Nham Tran, Alison Ricafrente, Joyce To, Maria Lund, Tania M. Marques, Margarida Gama-Carvalho, Krystyna Cwiklinski, John P. Dalton, Sheila Donnelly
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
R
Q
Acceso en línea:https://doaj.org/article/c491f3abaaee4078b8355327c7eadde9
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:c491f3abaaee4078b8355327c7eadde9
record_format dspace
spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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 AT nhamtran fasciolahepaticahijackshostmacrophagemirnamachinerytomodulateearlyinnateimmuneresponses
AT alisonricafrente fasciolahepaticahijackshostmacrophagemirnamachinerytomodulateearlyinnateimmuneresponses
AT joyceto fasciolahepaticahijackshostmacrophagemirnamachinerytomodulateearlyinnateimmuneresponses
AT marialund fasciolahepaticahijackshostmacrophagemirnamachinerytomodulateearlyinnateimmuneresponses
AT taniammarques fasciolahepaticahijackshostmacrophagemirnamachinerytomodulateearlyinnateimmuneresponses
AT margaridagamacarvalho fasciolahepaticahijackshostmacrophagemirnamachinerytomodulateearlyinnateimmuneresponses
AT krystynacwiklinski fasciolahepaticahijackshostmacrophagemirnamachinerytomodulateearlyinnateimmuneresponses
AT johnpdalton fasciolahepaticahijackshostmacrophagemirnamachinerytomodulateearlyinnateimmuneresponses
AT sheiladonnelly fasciolahepaticahijackshostmacrophagemirnamachinerytomodulateearlyinnateimmuneresponses
_version_ 1718392107580784640