Induction of Th2 responses and IgE is largely due to carbohydrates functioning as adjuvants on Schistosoma mansoni egg antigens

Infection with the helminth parasite Schistosoma mansoni induces a pronounc ed Th2-type response that is associated with significant IgE production. To better understand how the parasite drives these responses, we investigated the relative roles of proteins and carbohydrates in driving Th2-type and/o r IgE responses using a murine model of intranasal sensitization with solub le egg Ags (SEA) of Schistosoma mansoni. We found that repeated intranasal sensitization with soluble egg Ags led to the induction of both total and s pecific IgE production and nasal eosinophilia, By comparing the responses o f mice sensitized with SEA or metaperiodate-treated SEA we were able to dem onstrate that carbohydrates on SEA are the major inducers of IgE production and nasal recruitment of eosinophils, Mice sensitized with periodate-treat ed SEA displayed a significant decrease in both total and specific IgE leve ls in comparison to mice sensitized with native SEA. Furthermore, sensitiza tion of mice with periodate-treated SEA significantly reduced levels of Ag- specific IgG1, but had no effect on IgG2a production. Nasal lymphocytes fro m mice sensitized with native SEA, but not with periodate-treated SEA, prod uced IL-4, IL-5. and IL-10 when restimulated with native SEA in vitro. On t he other hand, lymphocytes from mice sensitized with periodate-treated SEA did not produce any of these same cytokines following in vitro restimulatio n, suggesting that carbohydrates were required for in vivo induction of Th2 response and for that of associated cytokine responses in this model. Last ly, competitive inhibition ELISA showed that although carbohydrates are req uired for SEA-specific IgE induction, they are not targets of the induced I gE response.