Specific recognition and cleavage of galectin-3 by Leishmania major through species-specific polygalactose epitope.
Lipophosphoglycan is a major surface molecule of Leishmania, protozoa parasites, which are the causative agents of leishmaniasis, a disease that annually afflicts millions of people worldwide. The oligosaccharide structures of lipophosphoglycan varies among species, and epitopes of these species-specific oligosaccharides are suggested to be implicated in the interaction of Leishmania with macrophages as well as species-specific tissue tropism observed in leishmaniasis. The recognition of the species-specific variation of oligosaccharides is likely to be mediated by host carbohydrate-binding proteins, lectins, but the identities of the lectins remain elusive. Galectin-3 is a mammalian soluble beta-galactoside-binding lectin and is expressed in macrophages, dendritic cells, and keratinocytes, as well as fibroblasts, all of which are present in the site of Leishmania infection. In this paper, we found that galectin-3 binds to lipophosphoglycan of Leishmania major but not to those of Leishmania donovani through L. major-specific polygalactose epitopes. Association of galectin-3 with L. major led to the cleavage of galectin-3, resulting in truncated galectin-3 containing the C-terminal lectin domain but lacking the N-terminal domain implicated in lectin oligomerization. This cleavage was inhibited by the galectin-3 antagonist lactose, as well as 1,10-ortho-phenanthroline, suggesting that galectin-3 is cleaved by zinc metalloproteases after its binding to lipophosphoglycans. The modulation of various innate immunity reactions by galectin-3 is affected by its oligomerization; therefore, we propose the L. major-specific truncation of galectin-3 may contribute to the species-specific immune responses induced by Leishmania.
Pelletier
Isabelle
I
Glycobiology Laboratory, Research Centre for Infectious Disease, Laval University Medical Centre, Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada.
Sato
Sachiko
S
D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology*; D001665:Binding Sites / Q000276:immunology; D002240:Carbohydrate Sequence; D002460:Cell Line; D000939:Epitopes / Q000502:physiology*; D037502:Galectin 3; D006028:Glycosphingolipids / Q000276:immunology; D007893:Leishmania donovani / Q000276:immunology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008969:Molecular Sequence Data; D051381:Rats; D013045:Species Specificity
D000943:Antigens, Differentiation; D000939:Epitopes; D037502:Galectin 3; D006028:Glycosphingolipids; C008290:lipophosphonoglycan