The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica: Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis.
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.
From the ‡School of Biological Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland;
Krystyna
K
Cwiklinski
From the ‡School of Biological Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland;
Eduardo
E
de la Torre-Escudero
§Área de Parasitología, Departamento de Biología Celular y Parasitología, Universitat de València, Burjassot, Valencia, Spain; ¶Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Universitat de València-Health Research Institute La Fe, Valencia, Spain;
Maria
M
Trelis
‖Departmento de Bioquímica y Biología Molecular, Universitat de València, Burjassot, Valencia, Spain;
Dolores
D
Bernal
**Laboratoire de santé Publique du Québec, Sainte-Anne-de-Bellevue, Canada;
Philippe J
PJ
Dufresne
From the ‡School of Biological Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland;
Gerard P
GP
Brennan
‡‡School of Biotechnology, Dublin City University, Dublin 9, Republic of Ireland;
Sandra
S
O'Neill
§§Departmento de Genética. Facultad de Medicina, UDELAR, Montevideo, Uruguay;
Jose
J
Tort
¶¶Centre for Genomic Research, University of Liverpool, UK;
Steve
S
Paterson
§Área de Parasitología, Departamento de Biología Celular y Parasitología, Universitat de València, Burjassot, Valencia, Spain; ¶Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Universitat de València-Health Research Institute La Fe, Valencia, Spain;
Antonio
A
Marcilla
From the ‡School of Biological Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland;
John P
JP
Dalton
From the ‡School of Biological Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland; ‖‖Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, UK mark.robinson@qub.ac.uk.
Mark W
MW
Robinson
D000818:Animals; D000067128:Extracellular Vesicles / Q000235:genetics / Q000378:metabolism*; D005210:Fasciola hepatica / Q000254:growth & development / Q000472:pathogenicity*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods
D015801:Helminth Proteins