Authors

Discussion

The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. It is important to note, however, that only the egg “losers” trapped in the host tissues, especially in the liver, are responsible for these manifestations. 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 small 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 big granuloma formation, but their life ends there.  Although these trapped eggs represent a dead end in the parasite life cycle, vast majority of transcriptomic, proteomic and secretomic studies attempting to describe the biology of the S. mansoni eggs have studied these liver-trapped “losers” instead of gut-attached “winners”. Thus, the fundamental question is if and possibly how the gene expression of the egg is affected by the surrounding tissues. In our study, we isolated S. mansoni eggs from the liver and intestinal tissues of experimentally infected mice, divided these eggs into mature and immature and compared their transcriptomic profiles. In addition, we evaluated viability of these eggs via hatching assays. Our results clearly show that gene expression in S. mansoni eggs is critically dependent on tissue localization. In addition to the crucial differences in expression 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. Among most differentially expressed genes of interest between these tissues are mitochondrial genes, 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 proposed as the primary egg immunomodulators, are, in fact, restricted to liver losers. 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 eggs, the up-regulated molecules probably represent the tools for successful passage to the external environment, in the case of the liver-trapped eggs, the high expression of immunomodulatory molecules may serve as a bait for the immune system for the benefit of the intestinal eggs.