LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune recognition

Timo K van den Berg, Henk Honing, Niels Franke, Alexandra van Remoortere, Wietske E C M Schiphorst, Fu-Tong Liu, André M Deelder, Richard D Cummings, Cornelis H Hokke, Irma van Die

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Although Gal beta 1-4GlcNAc (LacNAc) moieties are the most common constituents of N-linked glycans on vertebrate proteins, GalNAc beta 1-4GlcNAc (LacdiNAc, LDN)-containing glycans are widespread in invertebrates, such as helminths. We postulated that LDN might be a molecular pattern for recognition of helminth parasites by the immune system. Using LDN-based affinity chromatography and mass spectrometry, we have identified galectin-3 as the major LDN-binding protein in macrophages. By contrast, LDN binding was not observed with galectin-1. Surface plasmon resonance (SPR) analysis and a solid phase binding assay demonstrated that galectin-3 binds directly to neoglycoconjugates carrying LDN glycans. In addition, galectin-3 bound to Schistosoma mansoni soluble egg Ags and a mAb against the LDN glycan inhibited this binding, suggesting that LDN glycans within S. mansoni soluble egg Ags contribute to galectin-3 binding. Immunocytochemistry demonstrated high levels of galectin-3 in liver granulomas of S. mansoni-infected hamsters, and a colocalization of galectin-3 and LDN glycans was observed on the parasite eggshells. Finally, we demonstrate that galectin-3 can mediate recognition and phagocytosis of LDN-coated particles by macrophages. These findings provide evidence that LDN-glycans constitute a parasite pattern for galectin-3-mediated immune recognition.

Original languageEnglish
Pages (from-to)1902-7
Number of pages6
JournalJournal of Immunology
Volume173
Issue number3
Publication statusPublished - 1 Aug 2004

Cite this

van den Berg, T. K., Honing, H., Franke, N., van Remoortere, A., Schiphorst, W. E. C. M., Liu, F-T., ... van Die, I. (2004). LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune recognition. Journal of Immunology, 173(3), 1902-7.