Apoptosis Governs the Elimination of Schistosoma japonicum from the Non-Permissive Host Microtus fortis

摘要

The reed vole, Microtus fortis, is the only known mammalian host in which schistosomes of Schistosoma japonicum areunable to mature and cause significant pathogenesis. However, little is known about how Schistosoma japonicummaturation (and, therefore, the development of schistosomiasis) is prevented in M. fortis. In the present study, theultrastructure of 10 days post infection schistosomula from BALB/c mice and M. fortis were first compared using scanningelectron microscopy and transmission electron microscopy. Electron microscopic investigations showed growth retardationand ultrastructural differences in the tegument and sub-tegumental tissues as well as in the parenchymal cells ofschistosomula from M. fortis compared with those in BALB/c mice. Then, microarray analysis revealed significant differentialexpression between the schistosomula from the two rodents, with 3,293 down-regulated (by≥2-fold) and 71 up-regulated(≥2 fold) genes in schistosomula from the former. The up-regulated genes included a proliferation-related gene encodinggranulin (Grn) and tropomyosin. Genes that were down-regulated in schistosomula from M. fortis included apoptosis-inhibitedgenes encoding a baculoviral IAP repeat-containing protein (SjIAP) and cytokine-induced apoptosis inhibitor(SjCIAP), genes encoding molecules involved in insulin metabolism, long-chain fatty acid metabolism, signal transduction,the transforming growth factor (TGF) pathway, the Wnt pathway and in development. TUNEL (terminal deoxynucleotidyltransferase dUTP nick end labeling) and PI/Annexin V-FITC assays, caspase 3/7 activity analysis, and flow cytometry revealedthat the percentages of early apoptotic and late apoptotic and/or necrotic cells, as well as the level of caspase activity, inschistosomula from M. fortis were all significantly higher than in those from BALB/c mice.