Excreted/secreted Schistosoma mansoni venom allergen-like 9 (SmVAL9) modulates host extracellular matrix remodelling gene expression

Timothy P. Yoshino, Martha Brown, Xiao-Jun Wu, Colin John Jackson, Ramon Ocadiz-Ruiz, Iain Wyllie Chalmers, Marlen Kolb, Cornelis H. Hokke, Karl Francis Hoffmann

Allbwn ymchwil: Cyfraniad at gyfnodolynErthygladolygiad gan gymheiriaid

33 Dyfyniadau(SciVal)
306 Wedi eu Llwytho i Lawr (Pure)


The Schistosoma mansoni venom allergen-like (SmVAL) protein family consists of 29 members, each possessing a conserved a-b-a 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.
Iaith wreiddiolSaesneg
Tudalennau (o-i)551-563
Nifer y tudalennau13
CyfnodolynInternational Journal for Parasitology
Rhif cyhoeddi8
Dyddiad ar-lein cynnar21 Mai 2014
Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - Gorff 2014

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