Document Type

Journal Article

Publication Date

11-2015

Journal

Journal of Infectious Diseases

Volume

212

Issue

10

Inclusive Pages

1636-1645

DOI

10.1093/infdis/jiv291

Abstract

Background. Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterised the EV proteome and associated changes in cholangiocytes after EV uptake, and detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and IL-6 secretion was measured to assess the impact of EV internalization.

Results. EVs were identified in fluke culture medium and bile of infected hosts. EVs internalized by cholangiocytes drove cell proliferation and IL-6 secretion and induced changes in protein expression associated with endocytosis, wound repair and cancer. Antibodies to an O. viverrinitetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes.

Conclusions. This is the first time that EVs from a multicellular pathogen have been identified in host tissues. Our findings imply a role for O. viverrini EVs in pathogenesis and highlight an approach to vaccine development for this infectious cancer.

Comments

Reproduced with permission of Oxford University Press. The Journal of Infectious Diseases.

Supplementary Data available here.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Peer Reviewed

1

Open Access

1

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