Abstract
Extracellular Vesicles (EVs) are an integral component of cellular/organismal communication and have been found in the excreted/secreted (ES) products of both protozoan and metazoan parasites. Within the blood fluke schistosomes, EVs have been isolated from egg, schistosomula, and adult lifecycle stages. However, the role(s) that EVs have in shaping aspects of parasite biology and/or manipulating host interactions is poorly defined. Herein, we characterise the most abundant EV-enriched protein in Schistosoma mansoni tissue-migrating schistosomula (Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1)). Comparative sequence analysis demonstrates that lev1 orthologs are found in all published Schistosoma genomes, yet homologs are not found outside of the Schistosomatidae. Lifecycle expression analyses collectively reveal that smlev1 transcription peaks in cercariae, is male biased in adults, and is processed by alternative splicing in intra-mammalian lifecycle stages. Immunohistochemistry of cercariae using a polyclonal anti-recombinant SmLEV1 antiserum localises this protein to the pre-acetabular gland, with some disperse localisation to the surface of the parasite. S. mansoni-infected Ugandan fishermen exhibit a strong IgG1 response against SmLEV1 (dropping significantly after praziquantel treatment), with 11% of the cohort exhibiting an IgE response and minimal levels of detectable antigen-specific IgG4. Furthermore, mice vaccinated with rSmLEV1 show a slightly reduced parasite burden upon challenge infection and significantly reduced granuloma volumes, compared with control animals. Collectively, these results describe SmLEV1 as a Schistosomatidae-specific, EV-enriched immunogen. Further investigations are now necessary to uncover the full extent of SmLEV1's role in shaping schistosome EV function and definitive host relationships.
Highlights
Human schistosomiasis is caused by infection with platyhelminth species of the genus Schistosoma
We investigate the most abundant protein found within Extracellular Vesicles (EVs) released by early skin-stage schistosomes—Schistosoma mansoni Larval Extracellular Vesicle protein 1 (SmLEV1)
We show that the lev1 gene is only found in the schistosomes and closely related species and is most abundantly expressed during the early stages of human infection
Summary
Human schistosomiasis is caused by infection with platyhelminth species of the genus Schistosoma. Three main species are infectious to humans and include Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum [1]. Found in parts of Asia, South America, and Africa, and recently found in Corsica [2], schistosomiasis is the most important macroparasitic neglected tropical disease (NTD) in terms of its global health impact [3]. Schistosome infection is initiated when cercariae (free-living, non-feeding, aquatic larvae) penetrate human skin and transform into tissue migrating schistosomula. Concomitant with skin penetration, schistosomula release many excreted/secreted (ES) products to facilitate invasion and modulate the host immune response [4,5,6]. Membrane-bound EVs represent a component of schistosomula ES products and are enriched in proteins as well as small noncoding RNAs [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
