Induction of Th2 Responses and IgE Is Largely Due to Carbohydrates Functioning as Adjuvants onSchistosoma mansoniEgg Antigens

Abstract

Infection with the helminth parasite Schistosoma mansoni induces a pronounced 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/or IgE responses using a murine model of intranasal sensitization with soluble egg Ags (SEA) of Schistosoma mansoni. We found that repeated intranasal sensitization with soluble egg Ags led to the induction of both total and specific IgE production and nasal eosinophilia. By comparing the responses of mice sensitized with SEA or metaperiodate-treated SEA we were able to demonstrate that carbohydrates on SEA are the major inducers of IgE production and nasal recruitment of eosinophils. Mice sensitized with periodate-treated SEA displayed a significant decrease in both total and specific IgE levels in comparison to mice sensitized with native SEA. Furthermore, sensitization of mice with periodate-treated SEA significantly reduced levels of Ag-specific IgG1, but had no effect on IgG2a production. Nasal lymphocytes from mice sensitized with native SEA, but not with periodate-treated SEA, produced IL-4, IL-5, and IL-10 when restimulated with native SEA in vitro. On the other hand, lymphocytes from mice sensitized with periodate-treated SEA did not produce any of these same cytokines following in vitro restimulation, suggesting that carbohydrates were required for in vivo induction of Th2 response and for that of associated cytokine responses in this model. Lastly, competitive inhibition ELISA showed that although carbohydrates are required for SEA-specific IgE induction, they are not targets of the induced IgE response.

Estudo comparativo da expressão de carboidratos no sistema ovogranuloma hepático na esquistossomose humana e experimental

“…A partir da caracterização de carboidratos superficiais de parasitas durante o desenvolvimento da infecção 10,16 e através do mapeamento dos açucares residuais expostos na superfície dos ovos de S. mansoni 10,17 , foram obtidas importantes informações sobre a resposta imune do hospedeiro contra esse tipo de parasita 18 .…”

Schistosoma and Leishmania: An Untold Story of Coinfection

“…The immune responses elicited by both parasites, summarized in Figure 1 , are rather complex. During S. mansoni development in the vertebrate host, a predominant type 1 response is stimulated against cercariae penetration, schistosomula migration, and adult worms [ 40 , 41 , 42 ], followed mostly by a type 2 profile after oviposition begins [ 43 , 44 , 45 , 46 , 47 ]. In parallel, a regulatory response is developed, which takes over in the chronic phase of schistosomiasis [ 48 , 49 , 50 , 51 ].…”

“…Compared with tegumentary leishmaniasis, how schistosomiasis influences visceral leishmaniasis has not been addressed nearly as much. As pathogenesis in visceral leishmaniasis involves chemokine expression and the migration of immune cells in the liver and spleen [ 26 , 27 ], an infection with another parasite such as S. mansoni , which also alters cytokine profiles and cellular infiltration in these organs [ 47 ], is expected to heavily affect this process. In this context, it is worth mentioning a case report of enteropathic visceral leishmaniasis with concomitant S. mansoni infection, with persistent diarrhea, the presence of L. infantum amastigotes in duodenal biopsies, and relapses [ 64 ].…”

High-mannose glycans from Schistosoma mansoni eggs are important for priming of Th2 responses via Dectin-2 and prostaglandin E2

“…Many proteins in SEA are heavily glycosylated and their reported immunomodulatory effects are, in many cases, glycan dependent ( 11 , 12 ). Correspondingly, on DCs, SEA has been shown to interact with and signal through several glycan-binding C-type lectin receptors, such as the macrophage galactose-type lectin (MGL), CD209 (DC-SIGN), and CD206 (mannose receptor) to modulate TLR-induced cytokine production and T cell-priming capacity ( 13 – 17 ).…”