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.
Highlights
It has long been appreciated that schistosomes are capable of establishing long-lasting relationships with their intermediate snail and definitive mammalian hosts (Basch, 1991)
This increase in molecular mass indicated that eggderived native Schistosoma mansoni venom allergen-like 9 (SmVAL9) (nSmVAL9) is post-translationally modified and, as evidenced by the smear associated with the immunoreactive band, likely to be glycosylated
Two anti-recombinant SmVAL9 (rSmVAL9) immunoreactive proteins were found in the larval transformation proteins (LTPs) and Body samples, but not in the epidermal plates (EPs) preparation confirming that SmVAL9 was released into the immediate environment during larval transformation. These results indicated that most, if not all, SmVAL9 was found within non-epidermal plate containing material, but E/S SmVAL9 could adhere to cilia in intact miracidia
Summary
It has long been appreciated that schistosomes are capable of establishing long-lasting relationships with their intermediate snail and definitive mammalian hosts (Basch, 1991). While the molecular basis for these parasite/host interactions is not fully understood (Geyer and Hoffmann, 2012), a variety of schistosome biomolecules including glycans (Hokke and Deelder, 2001; van Die and Cummings, 2010), proteins (Han et al, 2009), small metabolites (Da’dara and Skelly, 2011) and even microRNAs (miRNAs) (Cheng et al, 2013) are postulated to be involved. Represents an important neglected tropical disease (NTD) targeted by international agencies for global elimination (Barry et al, 2013), identification and functional characterisation of the specific biomolecules utilised by schistosomes to orchestrate sustainable host interactions represents a rational approach in progressing novel chemotherapeutic/immunoprophylactic intervention strategies.
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