title: Excreted/secreted Schistosoma mansoni venom allergen-like 9 (SmVAL9) modulates host extracellular matrix remodelling gene expression.
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.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Yoshino
authors.affiliation: Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Room 3.31, Edward Llwyd Building, Penglais Campus, Aberystwyth SY23 3DA, UK.
authors.forename: Martha
authors.initials: M
authors.lastname: Brown
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wu
authors.affiliation: Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Room 3.31, Edward Llwyd Building, Penglais Campus, Aberystwyth SY23 3DA, UK.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Jackson
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Ocadiz-Ruiz
authors.affiliation: Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Room 3.31, Edward Llwyd Building, Penglais Campus, Aberystwyth SY23 3DA, UK.
authors.forename: Iain W
authors.initials: IW
authors.lastname: Chalmers
authors.affiliation: Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Room 3.31, Edward Llwyd Building, Penglais Campus, Aberystwyth SY23 3DA, UK.
authors.forename: Marlen
authors.initials: M
authors.lastname: Kolb
authors.affiliation: Department of Parasitology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
authors.affiliation: Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Room 3.31, Edward Llwyd Building, Penglais Campus, Aberystwyth SY23 3DA, UK. Electronic address: krh@aber.ac.uk.
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hoffmann
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001700:Biomphalaria; D002460:Cell Line; D005109:Extracellular Matrix / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D015801:Helminth Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000032:analysis; D012550:Schistosoma mansoni / Q000276:immunology / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D000485:Allergens; D015801:Helminth Proteins; D011134:Polysaccharides
keywords: Biomphalaria glabrata; Matrix metalloproteinase; Schistosoma mansoni; Venom allergen-like