Abstract
The reed vole, Microtus fortis, is the only known mammalian host in which schistosomes of Schistosoma japonicum are unable to mature and cause significant pathogenesis. However, little is known about how Schistosoma japonicum maturation (and, therefore, the development of schistosomiasis) is prevented in M. fortis. In the present study, the ultrastructure of 10 days post infection schistosomula from BALB/c mice and M. fortis were first compared using scanning electron microscopy and transmission electron microscopy. Electron microscopic investigations showed growth retardation and ultrastructural differences in the tegument and sub-tegumental tissues as well as in the parenchymal cells of schistosomula from M. fortis compared with those in BALB/c mice. Then, microarray analysis revealed significant differential expression 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 encoding granulin (Grn) and tropomyosin. Genes that were down-regulated in schistosomula from M. fortis included apoptosis-inhibited genes 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 deoxynucleotidyl transferase dUTP nick end labeling) and PI/Annexin V-FITC assays, caspase 3/7 activity analysis, and flow cytometry revealed that the percentages of early apoptotic and late apoptotic and/or necrotic cells, as well as the level of caspase activity, in schistosomula from M. fortis were all significantly higher than in those from BALB/c mice.
Highlights
Schistosomiasis is one of the most widespread and prevalent parasitic diseases of clinical and public health relevance
BALB/c mouse is a susceptible host for S. japonicum and nearly 70% of S. japonicum in BALB/c mice can complete the lifecycle
The ultrastructure was similar in appearance to that reported for lung schistosomula of S. japonicum [18]
Summary
Schistosomiasis is one of the most widespread and prevalent parasitic diseases of clinical and public health relevance. The reed vole, Microtus fortis, is the only mammal in which the growth, development and maturation of this schistosome is prevented, resulting in the failure of the parasite to mature and complete its life cycle [1,2,3]. Previous investigations have suggested that humoral and/or cellular immunity may play an important role in the restricted development of S. japonicum in M. fortis. Comparing differences in the molecular profiles of schistosomula from susceptible and non-permissive host species can provide important insights associated with schistosome development and, the nature of the anti-schistosomal mechanism that occurs within M. fortis. The analysis may identify key molecules which are essential for the survival and development of the schistosome, as well as providing a novel approach for defining potential vaccine candidates or drug targets for the control of schistosomiasis [6]
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