Abstract
Schistosomes express a family of integral membrane proteins, called tetraspanins (TSPs), in the outer surface membranes of the tegument. Two of these tetraspanins, Sm-TSP-1 and Sm-TSP-2, confer protection as vaccines in mice, and individuals who are naturally resistant to S. mansoni infection mount a strong IgG response to Sm-TSP-2. To determine their functions in the tegument of S. mansoni we used RNA interference to silence expression of Sm-tsp-1 and Sm-tsp-2 mRNAs. Soaking of parasites in Sm-tsp dsRNAs resulted in 61% (p = 0.009) and 74% (p = 0.009) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in adult worms, and 67%–75% (p = 0.011) and 69%–89% (p = 0.004) reductions in Sm-tsp-1 and Sm-tsp-2 transcription levels, respectively, in schistosomula compared to worms treated with irrelevant control (luciferase) dsRNA. Ultrastructural morphology of adult worms treated in vitro with Sm-tsp-2 dsRNA displayed a distinctly vacuolated and thinner tegument compared with controls. Schistosomula exposed in vitro to Sm-tsp-2 dsRNA had a significantly thinner and more vacuolated tegument, and morphology consistent with a failure of tegumentary invaginations to close. Injection of mice with schistosomula that had been electroporated with Sm-tsp-1 and Sm-tsp-2 dsRNAs resulted in 61% (p = 0.005) and 83% (p = 0.002) reductions in the numbers of parasites recovered from the mesenteries four weeks later when compared to dsRNA-treated controls. These results imply that tetraspanins play important structural roles impacting tegument development, maturation or stability.
Highlights
Schistosomes are parasitic trematodes that cause chronic infection in over 207 million people in 76 developing tropical countries
Cercariae penetrate the skin, shed their tails and transform into schistosomula, which reside in the dermis of the skin before entering the blood capillaries to migrate through the vasculature to the portal venous system where they mature into adult worms [4]
Among them are a group of membrane proteins called tetraspanins, which are highly expressed in the outer tegument membrane of adult schistosomes [12,13]
Summary
Schistosomes are parasitic trematodes that cause chronic infection in over 207 million people in 76 developing tropical countries. Humans become infected with schistosomes when they are exposed to free-living cercariae in fresh water. During transformation from cercaria to schistosomula, the outer surface of the tegument (the interface with the host) is remodeled from a single membrane with a prominent glycocalyx into an unusual double membrane (or ‘‘heptalaminate’’) structure [5]. This double membrane is widely believed to play an essential role in the ability of schistosomes to evade the host immune system, a characteristic that allows them to live for years within their hosts [6]. The generation of a large number of S. mansoni expressed sequence tags [9] and the recently completed genome sequence [10], in combination with advances in characterizing the tegument proteome has led to the discovery of many tegument
Sign-in/Register to view highlights & summary 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.
