Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses.

Tran, Nham ORCID: 0000-0001-7747-2530, Ricafrente, Alison, To, Joyce ORCID: 0000-0003-3482-4369, Lund, Maria, Marques, Tania M, Gama-Carvalho, Margarida, Cwiklinski, Krystyna ORCID: 0000-0001-5577-2735, Dalton, John P and Donnelly, Sheila ORCID: 0000-0003-2005-3698 (2021) Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses. Scientific reports, 11 (1). 6712-.

Access the full-text of this item by clicking on the Open Access link.

Official URL: http://dx.doi.org/10.1038/s41598-021-86125-1

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.

Item Type:	Article
Uncontrolled Keywords:	Macrophages, Animals, Fasciola hepatica, Fascioliasis, Disease Susceptibility, MicroRNAs, Signal Transduction, Gene Expression Regulation, RNA Interference, Host-Parasite Interactions, Immunity, Innate
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	24 Feb 2022 09:34
Last Modified:	14 Mar 2024 17:46
DOI:	10.1038/s41598-021-86125-1
Open Access URL:	https://www.nature.com/articles/s41598-021-86125-1
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3149569