PRJNA869546
Proteases and their inhibitors involved in Schistosoma mansoni egg-host interaction revealed by comparative transcriptomics with Fasciola hepatica eggs
Schistosoma mansoni eggs are the main causative agent of the pathological manifestation of schistosomiasis. The eggs are laid in the bloodstream of mammalian hosts, from where half of them migrate through the intestinal wall to the lumen and the remaining eggs usually become entrapped in the liver causing inflammation and fibrosis. The parasite-specific proteins enabling this egg tissue passage have not been well described yet. Conversely, the eggs of the related liver fluke Fasciola hepatica do not interact with host tissues as they are passively secreted from bile ducts into the gut lumen. In this study, we employed RNA-seq comparative transcriptomics of S. mansoni immature and mature eggs isolated from experimentally infected mice, and employed comparison to F. hepatica in vitro freshly laid and 5-days incubated eggs. We focused particularly on proteases and their inhibitors as molecules known to be essential for parasitic infections. We measured gene expression levels and performed differential expression analysis. We detected transcription of 135 and 117 proteases in S. mansoni and F. hepatica eggs, respectively, with 87 proteases being identified as orthologous between the two species. In contrast, we recorded only four orthologous inhibitors out of 21 and 16 identified in S. mansoni and F. hepatica eggs, respectively. Among others, we detected high expression of unique metalloproteases in S. mansoni eggs, such as aminopeptidase N 1, endothelin-converting enzyme 1, and several leishmanolysin-like proteins that have regulated transcription during the egg development. We identified highly transcribed protease inhibitors such as serpin and alpha-2-macroglobulin exclusive for S. mansoni eggs and a unique antistasin-like inhibitor in F. hepatica eggs. The distinct expression profiles of compared species reflect the different life strategies of studied flukes and ultimately revealed new potential players in the egg-host interplay, specifically in the regulation of host hemostasis, immunity, neovascularization and egg migration.