Role of carbohydrate moieties in recognition and uptake of allergens by innate immune cells

Allergens are initiators of both innate and adaptive immune responses. They are recognised at the site of entry by epithelial and dendritic cells (DCs), both of which activate innate inflammatory circuits that can collectively induce Th2 immune responses. In an attempt to have a better understanding of the role of carbohydrates in the recognition and uptake of allergens by the innate immune system, we defined common glycosylation patterns in major allergens like Der p 1, Fel d 1, Ara h 1, Ber e 1, Der p 2, Bla g 2 and Can f 1. Our data showed that all these allergens are glycosylated and that the main dominant sugars on allergens are 1-2, 1-3 and 1-6 mannose. We then investigated uptake and recognition of different allergen glycofroms (i.e. natural, hyper- and a-glycosylated) by DCs and lung epithelia. The deglycosylated preparation of Der p 1 exhibited minimal uptake by DCs compared to the natural and hyperglycosylated recombinant counterparts, with the latter being taken up more readily than the other preparations. Interestingly, our data also showed an increase in Thymic stromal lymphopoietin (TSLP) (known to drive DC maturation in support of Th2 responses) secretion by lung epithelia upon stimulation with natural Der p 1 which was carbohydrate dependent. Collectively, our data indicate that carbohydrate moieties on allergens play a vital role in their recognition by innate immune cells, implicating them in downstream deleterious Th2 cell activation and IgE production.