LacdiNAc- and LacNAc-containing glycans induce granulomas in an in vivo model for schistosome egg-induced hepatic granuloma formation

Schistosomes, major parasitic helminths, express numerous glycoconjugatesthat provoke humoral and cellular immune responses in the infectedhuman host. The main pathology in schistosomiasis is due tothe formation of granulomas around tissue-trapped eggs and theresulting organ damage. By using a mouse model of inductionof granulomas by hepatic implantation of antigen-coated beads,it has been determined that the glycan part of schistosomalsoluble egg antigens (SEA) initiates granulomogenesis. To identifywhich individual glycan elements in this complex SEA mixtureare granulomogenic, we have tested in the same mouse model conjugatesof various synthetic oligosaccharides characteristic for schistosomeeggs, including GalNAcß1-4GlcNAc (LacdiNAc, LDN),Galß1-4(Fuc1-3)GlcNAc (Lewis^x), Fuc1-2Fuc1-3GlcNAc(DF-Gn), and Fuc1-3GalNAcß1-4(Fuc1-3)GlcNAc (F-LDN-F).Ribonuclease (RNase) A and B, and different fetuin glycoformswere included as controls. Only beads that carry glycoconjugateswith terminal LacdiNAc or Galß1-4GlcNAc (LacNAc, LN)elements gave rise to granulomas, with macrophage, lymphocyte,and eosinophil levels similar to the granulomatous lesions causedby schistosome eggs in a natural infection. Uncoated beads,and beads coated with fucosylated glycoconjugates or glycoconjugateslacking terminally exposed Gal or GalNAc, only attracted a monolayerof macrophages. These results indicate that the formation ofhepatic granulomas is triggered specifically by glycoconjugateswhich carry terminal LacNAc or LacdiNAc, both constituents ofthe schistosome egg.