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

Area of Science:

• Immunology
• Glycobiology
• Parasitology

Background:

• Gal beta 1-4GlcNAc (LacNAc) is common in vertebrates, while GalNAc beta 1-4GlcNAc (LacdiNAc, LDN) is prevalent in invertebrates like helminths.
• The hypothesis that LDN acts as a molecular pattern for immune recognition of helminth parasites was investigated.

Purpose of the Study:

• To identify proteins that bind to LDN glycans in macrophages.
• To investigate the role of galectin-3 in recognizing helminth parasites via LDN glycans.
• To determine if galectin-3 mediates immune responses against LDN-expressing parasites.

Main Methods:

• LDN-based affinity chromatography and mass spectrometry to identify LDN-binding proteins.
• Surface plasmon resonance (SPR) and solid-phase binding assays to assess galectin-3 binding kinetics.
• Immunocytochemistry to localize galectin-3 and LDN glycans in infected tissues.
• Macrophage phagocytosis assays using LDN-coated particles.

Main Results:

• Galectin-3 was identified as the primary LDN-binding protein in macrophages, unlike galectin-1.
• Galectin-3 directly binds to LDN glycans and to Schistosoma mansoni soluble egg antigens.
• In vivo studies showed galectin-3 colocalization with LDN glycans on S. mansoni eggshells in infected liver granulomas.
• Galectin-3 facilitated macrophage recognition and phagocytosis of LDN-coated particles.

Conclusions:

• LDN glycans serve as a molecular pattern for galectin-3-mediated immune recognition of helminth parasites.
• Galectin-3 plays a crucial role in the innate immune response against helminths expressing LDN.
• These findings highlight the significance of LDN glycans in host-parasite interactions and immune evasion strategies.