The secretory antigens of Schistosoma mansoni and their involvement in the immune elimination of worms from rats.

Laboratory rats are able to expel schistosomes from the hepatic portal system around 28 days post-infection. Parasite-specific IgE titers rise and mast cells are recruited to the liver in large numbers, coincident with parasite expulsion. Since the worms appear viable prior to day 28, it is assumed that IgE production and mast cell degranulation are stimulated by antigens released by healthy parasites. The present study identified molecules released by adult worms, which could participate in stimulating IgE production and mast cell degranulation. By surgically transferring adult schistosomes from donor C57BL/6 mice to naive recipients of the same strain, it was possible to sustain viable parasite function for a period of 8 weeks. Larval development was bypassed, and since the recipient animals were exposed to healthy adult worms they mounted an antibody response directed against those antigens released by mature parasites only. Serum collected from the recipient mice (WTS) was used in western blotting studies to probe fractionated parasite protein. Twelve immunodominant moieties were identified ranging in molecular weight from 14 to 208 kDa. Eight of these antigens were immunolocalised to the tegument membrane or gastrodermis of adult worms. To investigate the nature of the IgE response during rat schistosomiasis, a longitudinal study was performed in which Fischer rats were exposed to male and female (mixed-sex), or male-only cercariae. Worms were recovered at days 28 and 42 post-infection to assess whether worm elimination had taken place. The levels of serum IgE and systemic mast cell protease (RMCP II; a mediator released following mast cell degranulation) were evaluated by ELISA. The results showed that total IgE production proceeded from day 21 and peaked at day 42 post-infection, whereas RMCP II release was high at days 28 and 35, but had diminished by day 42. Furthermore, it appeared that IgE levels were enhanced by products released from adult female worms, since mixed-sex infections induced greater IgE titers in comparison to male-only infections; this elevated IgE production was not attributed to egg secretions. Two dominant allergens Mw of 67 and 36-38 kDa were detected by western blotting using immunopurified IgE from infection serum. Parasite-specific IgE levels in the rat infection serum were quantified using a functional rat basophilic leukemia-serotonin release assay (RBL-SRA). Results from this assay not only corroborated evidence for enhanced IgE production following mixed-sex infections, but also modelled the complex interactions between IgE, mast cells and allergen. From the RBL-SRA it was concluded that female schistosomes were more allergenic than their male counterparts, and that this reactivity appeared to be directed against carbohydrate determinants. As very low levels of IgE are able to sensitise mast cells, and degranulation can be stimulated with microgram quantities of schistosome antigen, the results presented in this study support a role for mast cells and IgE in mediating worm elimination in rats.