Tearing Down the Wall: emu-miR-745-3p in Echinococcus multilocularis Exosomes Attenuates Host Liver Fibrosis to Permit Invasive Lesion Development.

BACKGROUND

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis (E. multilocularis), exhibits tumor-like, invasive growth in the liver. Unlike cystic echinococcosis, AE lesions are bordered by loose fibrosis, not a dense capsule. How the parasite weakens this host fibrotic response remians unknown.

METHODS

We identified functional miRNAs in parasite-derived exosomes via small RNA sequencing and multi-step screening, validated them using bioinformatics, luciferase assays, and in vitro studies in hepatic stellate cell studies (HSCs) and inhibited the target in vivo with AAV6-delivered TuD RNA in mice.

RESULTS

Exosomal emu-miR-745-3p from E. multilocularis targets DPP4 in HSCs, suppressing their activation and reducing fibrotic markers (α-SMA, COL1A1, TIMP1). In vivo inhibition of this miRNA increased perilesional fibrosis and capsule thickness, and decreased parasite burden.

CONCLUSIONS

E. multilocularis employs exosomal emu-miR-745-3p to attenuate host fibrotic encapsulation, facilitating invasive growth. The emu-miR-745-3p/DPP4 axis is a critical determinant of AE pathology and a potential target for novel anti-fibrotic therapeutics.