1 Leiden University Medical Center, UK
DiscussionHelminths express an abundance of proteins and lipids with specific and complex glycosylation patterns. Glycomics studies of helminth glycosylation are providing more and more insights into glycan and glycoconjugate expression of different helminth species. Schistosomes are one of the best studied parasitic helminths with respect to structural as well as functional glycomics. In the mammalian host antigenic glycans of larvae, worms and eggs of schistosomes induce specific antibodies to numerous glycan motifs, and glycans initiate or modulate innate immune responses and cellular uptake of glycoconjugates via host lectins. In the intermediate snail host specific glycans of miracidia and sporocysts interact with glycan-binding proteins in the hemolymph determining aspects of snail-schistosome compatibility.
To provide a clear map of schistosome glycosylation in support of functional studies of host-parasite glycobiology we applied mass spectrometric (MS) glycomics approaches to determine the expression profiles and structural identity of hundreds of glycans expressed during the schistosome life cycle. Striking shifts and switches in the expression of putative functional glycan motifs during during worm and egg development were identified suggesting various roles of glycans and associated anti-glycan responses during infection. In addition, we have generated a microarray of hundreds of N-, O-, and lipid-glycans covering the entire glycome of S. mansoni. The constructed glycan microarray was used to determine IgG and IgM to each glycan in a number of human and animal infection cohorts.
Using clear examples I will discuss how glycan motifs contribute to immunological properties of schistosome antigens, such as the immunomodulatory omega-1 glycoprotein. Also, based on cross-sectional and longitudinal glycan screens of antibodies in sera from natural and experimental schistosome infections, I will discuss the potential of antibodies against schistosome-specific Fucα1-2Fucα1-3-R glycan motifs in the development of glycan targets for vaccines and diagnostics. Glycomics-driven studies of helminths and helminth infections provide clear contributions to the development of novel therapeutics and control tools.