Egg secreted proteins: greater diversity than we thought

Abstract text

Introduction: The eggs produced by Schistosoma mansoni adults are responsible for the pathology in the host tissues. Immature eggs bind to the endothelial surface and until that point, they are immunologically inert. When mature, attached eggs actively induce host inflammatory processes to pass from the vasculature endothelial tissue into the gut environment. They evoke granuloma tissue formation - a highly organized multicellular cluster enriched with immune cells. Many eggs are washed out from mesenteric veins mostly to the liver, where granuloma formations cause significant pathologies.

Objectives: So far, little is known about the capability of the excretory/secretory products of eggs to stimulate these processes. Only a few secreted molecules have been experimentally studied and had their function revealed. So far, most of the attention has been devoted to egg-specific glycoproteins IPSE-1/alpha-1 and omega-1, among others promoting Th2 polarization. Nevertheless, the entire molecular composition of egg secretome and the roles of particular molecules remain unresolved.

Materials & methods: We are currently analyzing a portfolio of molecules produced by S. mansoni eggs by combining transcriptomic analysis and biochemical approaches. We focused on developed and undeveloped eggs isolated from the gut and liver tissue. Moreover, eggs of different S. mansoni geographical isolates are being analyzed in detail by bioinformatic pipeline in our lab as we have evidence that significant differences in the inflammatory reactions of rodent models are present.

Results & conclusion: Our preliminary data pointed out that gene expressions differ significantly based on the developmental stage of the eggs, tissue localization and S. mansoni strain. Our findings especially highlight two groups of proteins, the micro-exon gene (MEG) family and venom allergen-like (VAL) proteins, which are the most abundant molecules in egg transcriptome and their presence is stage and tissue localization dependent. Multi-isoform schistosome-specific proteins from MEG family encode some of the major secreted proteins with unknown functions with ~80% of the protein-coding region comprising short symmetric exons from 6-36 bp. VAL family shares a unique SCP/TAPS protein domain, which varies in length between 120 and 170 amino acids. Detailed immunohistochemical and biochemical studies are ongoing.