Winners vs. Losers – Comparative transcriptomic analysis of schistosoma mansoni mature and immature eggs from gut and liver

Abstract text

Introduction

The eggs of Schistosoma mansoni are the main cause of the clinical manifestations of schistosomiasis. It is important to note, however, that only the egg "losers" trapped in the host tissues, are responsible for these pathologies. After laying, the egg "winners", on the other hand, manage to attach to the endothelium of the mesenteric vein, and after a period of development, induce the growth of a granuloma which facilitates their passage through the intestinal wall to gut lumen. "Losers" carried with a blood stream to non-specific tissues also undergo full development and induce a granuloma formation, but their life ends there. Although trapped eggs represent a dead end in the life cycle, vast majority of transcriptomic and proteomic studies attempting to describe the biology of the eggs have studied these liver-trapped egg "losers" instead of gut-attached egg "winners".

Objectives

To assess if and how the gene expression of the egg is affected by the surrounding tissues.

Materials & Methods

We isolated eggs from the liver and intestinal tissues of experimentally infected mice, divided eggs into mature and immature and compared their transcriptomic profiles.

Results

Our results clearly show that gene expression in S. mansoni eggs is critically dependent on tissue localization. In addition to the crucial differences between eggs derived from the two tissues, the expression profiles of liver-derived eggs are very similar regardless of their developmental stage, whereas gut-derived eggs show remarkable changes during their maturation. The most differentially expressed genes of interest are the Venom allergen-like proteins (VALs), which, together with proteases and protease inhibitors, are substantially more active in intestinal eggs. In stark contrast, IPSE/alpha-1, omega-1, as well as the majority of micro-exon genes (MEGs), which are often discussed as the primary weapons of the egg-winners, are, in fact, restricted to liver losers.

Conclusion

We argue that such differential expression of many important groups of molecules directly reflects the environment in which the egg is located. While in the case of the gut-derived eggs, who attach themselves to the cell wall, the up-regulated molecules probably represent the tools for successful passage to the external environment, in the case of the liver-derived eggs, the specific expression is more likely a response to host defence systems and thus reflects the failure of these individuals.