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, Cornells H. Hokke, Irma Van Die

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133 Scopus citations

Abstract

Although Galβ1-4GlcNAc (LacNAc) moieties are the most common constituents of N-linked glycans on vertebrate proteins, GalNAcβ1-4GlcNAc (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 neoglycoconjagates 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 LBN-coated particles by macrophages. These findings provide evidence that LDN-glycans constitute a parasite pattern for galectin-3-mediated immune recognition.

Original languageEnglish (US)
Pages (from-to)1902-1907
Number of pages6
JournalJournal of Immunology
Volume173
Issue number3
StatePublished - Aug 1 2004

ASJC Scopus subject areas

  • Immunology

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    Van Den Berg, T. K., Honing, H., Franke, N., Van Remoortere, A., Schiphorst, W. E. C. M., Liu, F-T., Deelder, A. M., Cummings, R. D., Hokke, C. H., & Van Die, I. (2004). LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune recognition. Journal of Immunology, 173(3), 1902-1907.