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Published on: June 5, 2012
Excreted/secreted Schistosoma mansoni venom allergen-like 9 (SmVAL9) modulates host extracellular matrix remodelling
Timothy P Yoshino1, Martha Brown2, Xiao-Jun Wu1
1Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
Abstract:
The Schistosoma mansoni venom allergen-like (SmVAL) protein family consists of 29 members, each possessing a conserved α-β-α sandwich tertiary feature called the Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) domain. While the SmVALs have been found in both excretory/secretory (E/S) products and in intra/sub-tegumental (non-E/S) fractions, the role(s) of this family in host/parasite relationships or schistosome developmental processes remains poorly resolved. In order to begin quantifying SmVAL functional diversity or redundancy, dissecting the specific activity (ies) of individual family members is necessary. Towards this end, we present the characterisation of SmVAL9; a protein previously found enriched in both miracidia/sporocyst larval transformation proteins and in egg secretions. While our study confirms that SmVAL9 is indeed found in soluble egg products and miracidia/sporocyst larval transformation proteins, we find it to be maximally transcribed/translated in miracidia and subsequently down-regulated during in vitro sporocyst development. SmVAL9 localisation within sporocysts appears concentrated in parenchymal cells/vesicles as well as associated with larval germinal cells. Furthermore, we demonstrate that egg-derived SmVAL9 carries an N-linked glycan containing a schistosome-specific difucosyl element and is an immunogenic target during chronic murine schistosomiasis. Finally, we demonstrate that recombinant SmVAL9 affects the expression of extracellular matrix, remodelling matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) gene products in both Biomphalaria glabrata embryonic cell (BgMMP1) and Mus musculus bone marrow-derived macrophage (MmMMP2, MmMMP9, MmMMP12, MmMMP13, MmMMP14, MmMMP28, TIMP1 and TIMP2) in vitro cultures. These findings importantly suggest that excreted/secreted SmVAL9 participates in tissue reorganisation/extracellular matrix remodelling during intra-mammalian egg translocation, miracidia infection and intra-molluscan sporocyst development/migration.
Insights
Schistosoma mansoni venom allergen-like 9 (SmVAL9) protein is secreted by eggs and larvae, impacting host tissue remodeling. This study characterizes SmVAL9, revealing its role in parasite development and host-parasite interactions.
Area of Science:
- Parasitology
- Molecular Biology
- Biochemistry
Background:
- The Schistosoma mansoni venom allergen-like (SmVAL) protein family, comprising 29 members with a conserved SCP/TAPS domain, plays roles in host-parasite interactions and parasite development.
- The specific functions of individual SmVAL proteins, including their involvement in excretory/secretory (E/S) products and non-E/S fractions, remain largely uncharacterized.
Purpose of the Study:
- To characterize the Schistosoma mansoni venom allergen-like 9 (SmVAL9) protein.
- To investigate the expression, localization, and functional activities of SmVAL9 during different life cycle stages and its impact on host cells.
Main Methods:
- Quantitative analysis of SmVAL9 transcription and translation across parasite stages.
- Immunofluorescence microscopy for SmVAL9 localization within sporocysts.
- Characterization of SmVAL9 glycosylation and immunogenicity in infected mice.
- In vitro assays using recombinant SmVAL9 to assess its effect on host cell gene expression (MMP and TIMP).
Main Results:
- SmVAL9 is maximally transcribed/translated in miracidia and down-regulated during in vitro sporocyst development.
- SmVAL9 localizes to parenchymal cells, vesicles, and germinal cells within sporocysts.
- Egg-derived SmVAL9 is N-linked glycosylated with a schistosome-specific difucosyl element and is immunogenic in chronic murine schistosomiasis.
- Recombinant SmVAL9 alters the expression of extracellular matrix remodeling genes (MMPs and TIMPs) in snail and mouse cell cultures.
Conclusions:
- Excreted/secreted SmVAL9 is involved in tissue reorganization and extracellular matrix remodeling during critical stages of the schistosome life cycle, including egg translocation, miracidia infection, and sporocyst development/migration.
- SmVAL9 represents a potential target for therapeutic intervention due to its immunogenicity and role in parasite development and host tissue interaction.
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