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

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149 Citations (Scopus)

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)1902-1907
Number of pages6
JournalJournal of immunology (Baltimore, Md.
Volume173
Issue number3
DOIs
Publication statusPublished - 1 Aug 2004

Keywords

  • Animals
  • Antigens, Helminth/chemistry
  • Cell Line
  • Cricetinae
  • Disaccharides/immunology
  • Galectin 1/metabolism
  • Galectin 3/genetics
  • Glycoconjugates/immunology
  • Humans
  • Lactose/analogs & derivatives
  • Macrophages/immunology
  • Male
  • Mesocricetus
  • Phagocytosis
  • Polysaccharides/immunology
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins/immunology
  • Schistosoma mansoni/immunology
  • Schistosomiasis mansoni/immunology
  • Surface Plasmon Resonance

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