LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune recognition.
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.
van den Berg
Timo K
TK
Department of Molecular Cell Biology and Immunology, Vrige University University Medical Center, Amsterdam, The Netherlands. t.vandenberg@vumc.nl
Honing
Henk
H
Franke
Niels
N
van Remoortere
Alexandra
A
Schiphorst
Wietske E C M
WE
Liu
Fu-Tong
FT
Deelder
André M
AM
Cummings
Richard D
RD
Hokke
Cornelis H
CH
van Die
Irma
I
D000818:Animals; D000947:Antigens, Helminth / Q000737:chemistry / Q000276:immunology*; D002460:Cell Line; D006224:Cricetinae; D004187:Disaccharides / Q000276:immunology*; D037483:Galectin 1 / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006001:Glycoconjugates / Q000276:immunology*; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D010587:Phagocytosis; D011134:Polysaccharides / Q000276:immunology*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology; D020349:Surface Plasmon Resonance
D000947:Antigens, Helminth; D004187:Disaccharides; D037483:Galectin 1; D037502:Galectin 3; D006001:Glycoconjugates; D011134:Polysaccharides; D011993:Recombinant Fusion Proteins; C093701:N-acetylgalactosaminyl-1-4-N-acetylglucosamine; D007785:Lactose