Research
The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica: Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis* [S]

https://doi.org/10.1074/mcp.M115.053934Get rights and content
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Extracellular vesicles (EVs) released by parasites have important roles in establishing and maintaining infection. Analysis of the soluble and vesicular secretions of adult Fasciola hepatica has established a definitive characterization of the total secretome of this zoonotic parasite. Fasciola secretes at least two subpopulations of EVs that differ according to size, cargo molecules and site of release from the parasite. The larger EVs are released from the specialized cells that line the parasite gastrodermus and contain the zymogen of the 37 kDa cathepsin L peptidase that performs a digestive function. The smaller exosome-like vesicle population originate from multivesicular bodies within the tegumental syncytium and carry many previously described immunomodulatory molecules that could be delivered into host cells. By integrating our proteomics data with recently available transcriptomic data sets we have detailed the pathways involved with EV biogenesis in F. hepatica and propose that the small exosome biogenesis occurs via ESCRT-dependent MVB formation in the tegumental syncytium before being shed from the apical plasma membrane. Furthermore, we found that the molecular “machinery” required for EV biogenesis is constitutively expressed across the intramammalian development stages of the parasite. By contrast, the cargo molecules packaged within the EVs are developmentally regulated, most likely to facilitate the parasites migration through host tissue and to counteract host immune attack.

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* This work was supported by the Biotechnology and Biological Sciences Research Council, grant BB/L019612/1 (to M.W.R) and the European Research Council, grant 2012 AdG (to J.P.D).

Author contributions: A.M., J.P.D., and M.W.R. designed research; K.C., E.d., M.T., D.B., P.J.D., G.P.B., A.M., and M.W.R. performed research; K.C., M.T., D.B., P.J.D., G.P.B., S.O., J.T., S.P., A.M., J.P.D., and M.W.R. contributed new reagents or analytic tools; K.C., E.d., M.T., D.B., P.J.D., S.P., A.M., J.P.D., and M.W.R. analyzed data; K.C., E.d., J.P.D., and M.W.R. wrote the paper.

Data access statement: Genomic and transcriptomic data are available from the European Nucleotide Archive under the accession numbers PRJEB6687 and PRJEB6904 respectively. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD002570.

[S]

This article contains supplemental Figs. S1, S2 and Tables S1 to S4.

b

These authors contributed equally.