Extracellular Vesicles from Parasitic Helminths Contain Specific Excretory/Secretory Proteins and Are Internalized in Intestinal Host Cells

Abstract

The study of host-parasite interactions has increased considerably in the last decades, with many studies focusing on the identification of parasite molecules (i.e. surface or excretory/secretory proteins (ESP)) as potential targets for new specific treatments and/or diagnostic tools. In parallel, in the last few years there have been significant advances in the field of extracellular vesicles research. Among these vesicles, exosomes of endocytic origin, with a characteristic size ranging from 30–100 nm, carry several atypical secreted proteins in different organisms, including parasitic protozoa. Here, we present experimental evidence for the existence of exosome-like vesicles in parasitic helminths, specifically the trematodes Echinostoma caproni and Fasciola hepatica. These microvesicles are actively released by the parasites and are taken up by host cells. Trematode extracellular vesicles contain most of the proteins previously identified as components of ESP, as confirmed by proteomic, immunogold labeling and electron microscopy studies. In addition to parasitic proteins, we also identify host proteins in these structures. The existence of extracellular vesicles explains the secretion of atypical proteins in trematodes, and the demonstration of their uptake by host cells suggests an important role for these structures in host-parasite communication, as described for other infectious agents.

Development of Two Antibody Detection Enzyme-Linked Immunosorbent Assays for Serodiagnosis of Human Chronic Fascioliasis

“…However, based on the performance of the recombinant proteins using sera from animals with acute infections, it is likely that the in-house ELISAs will be similarly useful for diagnosis at early stages of human infections. Moreover, very interesting studies have identified ferritin-like and tegument-associated proteins in the vomitus and exosome-like vesicles of trematodes (37)(38)(39)(40). These extracellular vesicles account for 52% of the F. hepatica secretomes (39)(40)(41)(42), providing another explanation for the secretion of atypical proteins in helminths and their exposure to the host interface.…”

“…Moreover, very interesting studies have identified ferritin-like and tegument-associated proteins in the vomitus and exosome-like vesicles of trematodes (37)(38)(39)(40). These extracellular vesicles account for 52% of the F. hepatica secretomes (39)(40)(41)(42), providing another explanation for the secretion of atypical proteins in helminths and their exposure to the host interface. In our study, only 2 (3.3%) true-positive cases (positive in CE) fell below the cutoff value with FhFtn-1, whereas 5 (8.3%) truepositive cases were recorded as negative with FhTP16.5.…”

Extracellular vesicle-mediated communication in host-parasite interactions: insight from Fasciola hepatica

“…Whilst EVs secreted by helminths can be internalized by host cells and regulate host immune and inflammatory responses (2)(3)(4)(5)10), it is unclear to what extent Fasciola EVs contribute to maintaining a Th2/regulatory environment that is permissive to fluke survival and reproduction. Once we gain a better understanding of these issues, the selective disruption of key pathways involved in EV biogenesis, or blocking the EV-driven delivery of parasite immunomodulators to host cells, might prove to be an efficient way to achieve parasite control in the future.…”

Solution Structure, Membrane Interactions, and Protein Binding Partners of the Tetraspanin Sm-TSP-2, a Vaccine Antigen from the Human Blood Fluke Schistosoma mansoni

“…A large quantity of TSPs are released from the cell in exosomes (3, 48 -50), and it has been suggested that TSPs orchestrate changes in the plasma membrane leading to the formation and budding of exosomes from the cell (4). Although schistosome exosomes have not yet been described, they have been found in related species Echinostoma caproni and Fasciola hepatica (52) as well as in the nematode Caenorhabditis elegans (53). Using Exocarta (54), all proteins identified as potential members of a Sm-TSP-2 TEM had homologues that are known constituents of exosomes, the sole exception being Sm29, a protein unique to schistosomes.…”