Natural and synthetic glycan arrays for probing interactions of the innate and adaptive immune system with zwitterionic oligosaccharides

Invertebrate glycans are often ‘foreign’ to mammals, but many invertebrates are parasites which also immunomodulate the responses of the host, while invertebrate cell lines are potential ‘cell factories’ for production of secreted glycoprotein biopharmaceuticals. However, if we wish to investigate the innate or adaptive immune response of mammals to invertebrate glycoconjugates, a methodological hurdle is that most glycan arrays primarily focus on mammalian structures and not on those from other species. We are addressing this gap in the glycobiological toolbox by preparing arrays of either natural glycans from invertebrates or synthetic glycoconjugates displaying invertebrate glyco-epitopes. To date we have printed (i) the neutral and anionic pools of N-glycans from honeybee royal jelly, (ii) the native and hydrofluoric acid-treated neutral pools of N-glycans from the canine heartworm, (iii) fractions of N-glycans from the canine heartworm, (iii) mono- and disaccharides modified with zwitterionic phosphoethanolamine or phosphorylcholine and (iv) fucosylated and non-fucosylated forms of chitobiose and LacdiNAc. These pools, fractions or compounds were probed with various lectins, pentraxins or antibodies. We show that human serum amyloid P binds glycans derived from royal jelly (the food for honeybee queens, but also used as a beauty product), while human C-reactive protein (CRP) interacts with the glycans of the canine heartworm (a mosquito-borne parasite). On the other hand, short phosphorylcholine-modified glycoconjugates are recognized not only by CRP, but by IgG and IgM in the sera of some nematode-infected animals. Not only are such arrays complementary to current resources, but they have high potential to yield new insights into the glycan-mediated interactions of invertebrates with mammals. Support or Funding Information This work was supported by the Austrian Science Fund (FWF) by grants to I.B.H.W., S.Y., A.H. and K.P.