Schistosome N‐glycans containing core α3‐fucose and core β2‐xylose epitopes are strong inducers of Th2 responses in mice

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Abstract
During murine schistosomiasis, egg‐derived glycoconjugates play a key role in skewing the immune response towards a Th2 phenotype. Among the candidates responsible for this effect, complex‐type N‐glycans containing the core α3‐fucose and core β2‐xylose determinants, two glycan epitopes found in some invertebrate‐ and plant‐derived allergens, may be important. Here, we show that core α3‐fucose and core β2‐xylose determinants are expressed in the different developmental stages of Schistosoma mansoni, particularly in the excretory‐secretory systems of schistosomula and adult worms and in eggs deposited in the liver. Glycosyltransferase assays confirmed the presence of core α3‐fucosyltransferase and core β2‐xylosyltransferase activities in egg extracts. Using a model of immunization with pulsed dendritic cells, we show that egg‐derived glycoproteins containing the core α3‐fucose and core β2‐xylose determinants generate a strong Th2‐biased cellular response in mice and that the glycan moieties of this extract are important in this effect. During murine infection, these complex‐type N‐glycans induce a glycan‐specific Th2 cellular response and elicit T‐dependent anti‐core α3‐fucose and anti‐core β2‐xylose IgG1 (a Th2‐associated isotype), but not IgG2b (a Th1‐associated isotype) Ab. Taken together, our results point out theimportance of core fucosylated/xylosylated N‐glycans in the Th2 immune response during murine schistosomiasis.