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Updated: Aug 24, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses
Nham Tran1, Alison Ricafrente2, Joyce To2
1School of Biomedical Engineering, Faculty of Engineering and Information Technology, The University of Technology Sydney, Ultimo, NSW, Australia.
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.
Insights
The liver fluke Fasciola hepatica releases microRNAs (miRNAs) that suppress host immune cells. Parasitic miRNA fhe-miR-125b mimics host miRNAs to block inflammatory responses, aiding infection.
Area of Science:
- Parasitology
- Immunology
- Molecular Biology
Background:
- Fasciola hepatica is a significant helminth parasite affecting humans and livestock worldwide.
- This parasite rapidly manipulates host innate immunity, specifically targeting macrophages, crucial for early defense.
- Suppression of pro-inflammatory responses by host macrophages is observed shortly after infection.
Purpose of the Study:
- To investigate the mechanism by which Fasciola hepatica regulates host innate immune responses.
- To identify specific parasite-derived molecules involved in immune evasion.
- To elucidate how these molecules interfere with macrophage function.
Main Methods:
- Analysis of micro(mi)RNA content in macrophages from infected animals.
- Identification and characterization of abundant parasite-derived miRNAs, particularly fhe-miR-125b.
- Investigation of fhe-miR-125b's mechanism of action, including exosome-mediated release and interaction with host Argonaut protein (Ago-2).
Main Results:
- Macrophages from infected animals were found to be enriched with parasite-derived miRNAs.
- The micro(mi)RNA fhe-miR-125b, homologous to human hsa-miR-125b, was identified as a key player.
- Parasitic fhe-miR-125b was shown to load onto host Ago-2 and mimic host miR-125b, downregulating inflammatory cytokine production.
Conclusions:
- Fasciola hepatica utilizes parasite-derived micro(mi)RNAs, such as fhe-miR-125b, to disarm host macrophages.
- This molecular mimicry allows the parasite to evade early immune detection and establish infection.
- Hijacking host miRNA machinery represents a fundamental strategy for helminth parasites to ensure successful infection.
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