LacdiNAc-Glycans Constitute a Parasite Pattern for Galectin-3-Mediated Immune Recognition

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 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.

The Galectin CvGal1 from the Eastern Oyster (Crassostrea virginica) Binds to Blood Group A Oligosaccharides on the Hemocyte Surface*

“…Among these, the galectin CGL2 from inky cap mushroom Coprinus cinereus displays in vitro specificity for blood group A oligosaccharides (39,40), whereas the mammalian galectins 2-4 and 8 can recognize A and B oligosaccharides in a concentration-dependent manner (36,37). Although not specific for A oligosaccharides, some galectins can recognize nonreducing terminal GalNAc moieties in exogenous ligands, such as the human galectin-3 that binds to soluble and egg shell-associated glycans of the parasite helminth Schistosoma mansoni displaying GalNAc␤1-4GlcNAc (41). Furthermore, recent studies have shown that in vivo CGL2 actually binds the "galactosylated core fucose" glycotope (42), whereas CGL3, another galectin from C. cinereus, recognizes N-acetylhexosamines (HexNAc) such as in GlcNAc-GlcNAc or GalNAc-GlcNAc in vitro but not lactose (43).…”

Lack of galectin‐3 alters the balance of innate immune cytokines and confers resistance to Rhodococcus equi infection

“…As a result of its ability to recognize glycans containing b-galactoside, galectin-3 binds to glycoconjugates synthesized by several pathogens such as Mycobacterium tuberculosis [16], Leishmania major [17], Trypanosoma cruzi [18], Schistosoma mansoni [19] and Candida albicans [20]. Recently, galectin-3 and TLR2 have been found to be associated in C. albicans-infected differentiated macrophages, an association that has been considered essential for TLR2-dependent cytokine production in response to the fungal infection [21].…”

“…Extracellular galectin-3 is able to activate cells [4][5][6][7][8][9] cell-cell and cell-extracellular matrix interactions [10][11][12], and induce phagocyte migration [13]. However, galectin-3 also functions inside the cells and can contribute to macrophage functions that are essential in the cellular response during the infectious process, such as cell survival [14] and phagocytosis [15].As a result of its ability to recognize glycans containing b-galactoside, galectin-3 binds to glycoconjugates synthesized by several pathogens such as Mycobacterium tuberculosis [16], Leishmania major [17], Trypanosoma cruzi [18], Schistosoma mansoni [19] and Candida albicans [20]. Recently, galectin-3 and TLR2 have been found to be associated in C. albicans-infected differentiated macrophages, an association that has been considered essential for TLR2-dependent cytokine production in response to the fungal infection [21].…”

Galectin-3 Is a Negative Regulator of Lipopolysaccharide-Mediated Inflammation

“…It has been suggested that galectin-3 may serve as a pathogen pattern recognition receptor to visualize PAMPs from bacteria (19,20), parasites (21,22), and fungi (23,24). Moreover, it has been reported that galectin-3 interacts with LPS via both NЈ and CЈ terminals (25).…”