Galectin-3 Induces Death of Candida Species Expressing Specific β-1,2-Linked Mannans

Abstract

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 β-1,2-linked oligomannans on the cell surface, but did not bind Saccharomyces cerevisiae that lacks β-1,2-linked oligomannans. Surprisingly, binding directly induced death of Candida species containing specific β-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.

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).…”

The Cek1‑mediated MAP kinase pathway regulates exposure of α‑1,2 and β‑1,2‑mannosides in the cell wall ofCandida albicansmodulating immune recognition

“…79 In addition to the indicated roles of this lectin in promoting phagocytic uptake and prevention of microbial dissemination, galectin-3 has a direct fungicidal activity upon binding to the specific b-M present in the C. albicans cell wall. 24 In this work, we show that the increased binding of cek1 mutants is partially impaired by lactose (a blocking agent of galectins binding site) suggesting a role for this receptor in cek1 recognition. Through western blotting and immunofluorescence analysis of C. albicans interaction with murine macrophages, we uncovered an increased stimulation of galectin-3 secretion caused by cek1 infection, when compared to the wild type strain, and possible increased expression at the macrophage membrane and cytoplasm.…”

“…24 Given the increased detection of b-M in the cell surface of cek1 mutants, we analyzed whether galectin-3 could be relevant in this interaction. We first assessed the effect of lactose on C. albicans binding to murine macrophages, given its role as inhibitor of galectins carbohydrate binding site.…”

“…6,20 It participates in a variety of cellular processes through either intracellular or extracellular mechanisms. 21 Intracellular galectin-3 regulates cell survival, pre-mRNA splicing and phagocytosis 22 while extracellular galectin-3 modulates cell adhesion, activation and migration 23 and it has been shown to possess a direct fungicidal activity against C. albicans through recognition of b-M. 24 Adaptation to a changing environment and coping with host defenses is vital for pathogen survival. MAPK-mediated signal transduction pathways are mechanisms that organisms employ for this purpose.…”

Fungal killing by mammalian phagocytic cells

“…However, studies with knockout mice and mutant C. albicans strains have shown the importance of TLR4 [10]. Galectin-3 is a β-1,2 mannan receptor that specifically recognizes the pathogenic yeast C. albicans but not the non-pathogenic Saccharomyces cerevisiae [11] and to exerts direct fungicidal effect [12]. TLR1 and TLR6, known to form heterodimers with TLR2, have been recently shown to have no or mild effect on macrophage recognition of C. albicans [13].…”