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-1,2-Linked Mannans1


* Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, School of Medicine, University of California, Los Angeles, CA 90095; and
Department of Dermatology, School of Medicine, University of California Davis, Sacramento, CA 95817
Lectins play a critical role in host protection against infection. The galectin family of lectins recognizes saccharide ligands on a variety of microbial pathogens, including viruses, bacteria, and parasites. Galectin-3, a galectin expressed by macrophages, dendritic cells, and epithelial cells, binds bacterial and parasitic pathogens including Leishmania major, Trypanosoma cruzi, and Neisseria gonorrhoeae. However, there have been no reports of galectins having direct effects on microbial viability. We found that galectin-3 bound only to Candida albicans species that bear
-1,2-linked oligomannans on the cell surface, but did not bind Saccharomyces cerevisiae that lacks
-1,2-linked oligomannans. Surprisingly, binding directly induced death of Candida species containing specific
-1,2-linked oligomannosides. Thus, galectin-3 can act as a pattern recognition receptor that recognizes a unique pathogen-specific oligosaccharide sequence. This is the first description of antimicrobial activity for a member of the galectin family of mammalian lectins; unlike other lectins of the innate immune system that promote opsonization and phagocytosis, galectin-3 has direct fungicidal activity against opportunistic fungal pathogens.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health (NIH) Grant AI07323 (Microbial Pathogenesis Training Grant) (to L.K.), NIH Grant R01 GM63281 (to L.G.B.), and R01 AI20958 and R01 AI39620 (to F.-T.L.).
2 Address correspondence and reprint requests to Dr. Linda G. Baum, Department of Pathology and Laboratory Medicine, School of Medicine, University of California Los Angeles School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095. E-mail address: lbaum{at}mednet.ucla.edu
3 Abbreviations used in this paper: PRR, pattern recognition receptor; PAMP, pathogen-associated molecular pattern; CRD, carbohydrate recognition domain; SA, streptavidin; DTAF, (4,6-dichlorotriazinyl) aminofluorescein.
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