Specific Recognition of Leishmania major Poly-β-galactosyl Epitopes by Galectin-9: POSSIBLE IMPLICATION OF GALECTIN-9 IN INTERACTION BETWEEN L. MAJOR AND HOST CELLS

Isabelle Pelletier,Tomomi Hashidate,Tadasu Urashima,Nozomu Nishi,Takanori Nakamura,Masamitsu Futai,Yoichiro Arata,Ken-Ichi Kasai,Mitsuomi Hirashima,Jun Hirabayashi,Sachiko Sato

doi:10.1074/jbc.m302693200

Abstract

Leishmania parasites are the causative agents of leishmaniasis, manifesting itself in a species-specific manner. The glycan epitopes on the parasite are suggested to be involved in the Leishmania pathogenesis. One of such established species-unique glycan structures is the poly-beta-galactosyl epitope (Galbeta1-3)n found on L. major, which can develop cutaneous infections with strong inflammatory responses. Interestingly, the polygalactosyl epitope is also suggested to be involved in the development of the parasites in its host vector, sand fly. Thus, the recognition of the galactosyl epitope by lectins expressed in host or sand fly should be implicated in the species-specific manifestations of leishmaniasis and in the parasite life cycle, respectively. We recently reported that one host beta-galactoside-binding protein, galectin-3, can distinguish L. major from the other species through its binding to the poly-beta-galactosyl epitope, proposing a role for galectin-3 as an immunomodulator that could influence the L. major-specific immune responses in leishmaniasis. Here we report that galectin-9 can also recognize L. major by binding to the L. major-specific polygalactosyl epitope. Frontal affinity analysis with different lengths of poly-beta-galactosyllactose revealed that the galectin-9 affinity for polygalactose was enhanced in proportion to the number of Galbeta1-3 units present. Even though both galectins have comparable affinities toward the polygalactosyl epitopes, only galectin-9 can promote the interaction between L. major and macrophages, suggesting distinctive roles for the galectins in the L. major-specific development of leishmaniasis in the host.

Highlights

Leishmania parasites are the causative agents of leishmaniasis, manifesting itself in a species-specific manner
Our previous paper [16] and the present results obtained by classical biological assays with galectins and by Frontal Affinity Chromatography (FAC) analysis demonstrate that galectin-3 and -9 recognize L. major but not L. donovani through L. major-specific poly-␤-galactosyl epitopes
The promastigotes are engulfed by macrophages where they differentiate into nonflagellated Leishmania amastigotes and multiply [36, 60]

Summary

Introduction

Leishmania parasites are the causative agents of leishmaniasis, manifesting itself in a species-specific manner. Frontal affinity analysis with different lengths of poly-␤-galactosyllactose revealed that the galectin-9 affinity for polygalactose was enhanced in proportion to the number of Gal␤1–3 units present Even though both galectins have comparable affinities toward the polygalactosyl epitopes, only galectin-9 can promote the interaction between L. major and macrophages, suggesting distinctive roles for the galectins in the L. major-specific development of leishmaniasis in the host. A number of pathogenic entities express glycoconjugates containing ␤-galactosides, either similar to those of the host cells or unique to pathogens, such as the polygalactosyl epitope on protozoa Leishmania major [13, 14] Questions such as whether some galectins can play roles as “nonself ” or pathogen-recognizing molecules have recently emerged. It has been speculated that the differences in the galectin CRD arrangements influence the cross-linking mode of the galectin ligand and contribute to their functions (24 –26), such a possibility remains to be investigated

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Results

Conclusion