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Specific Recognition of Candida albicans by Macrophages Requires Galectin-3 to Discriminate Saccharomyces cerevisiae and Needs Association with TLR2 for Signaling¹

Thierry Jouault^2,*, Miryam El Abed-El Behi^*, María Martínez-Esparza, Laetitia Breuilh, Pierre-André Trinel^*, Mathias Chamaillard, Francois Trottein and Daniel Poulain^*

^* Institut National de la Santé et de la Recherche Médicale, Unité 799 and Université de Lille II, Institut National de la Santé et de la Recherche Médicale, Unité 547, Institut Pasteur, and Institut National de la Santé et de la Recherche Médicale, Unité 795, Lille, France; and Departamento de Bioquímica B e Inmunología, Facultad de Medicina, Universidad de Murcia, Murcia, Spain

Stimulation of cells of the macrophage lineage is a crucial step in the sensing of yeasts by the immune system. Glycans present in both Candida albicans and Saccharomyces cerevisiae cell walls have been shown to act as ligands for different receptors leading to different stimulating pathways, some of which need receptor co-involvement. However, among these ligand-receptor couples, none has been shown to discriminate the pathogenic yeast C. albicans. We explored the role of galectin-3, which binds C. albicans -1,2 mannosides. These glycans are specifically and prominently expressed at the surface of C. albicans but not on S. cerevisiae. Using a mouse cell line and galectin-3-deleted cells from knockout mice, we demonstrated a specific enhancement of the cellular response to C. albicans compared with S. cerevisiae, which depended on galectin-3 expression. However, galectin-3 was not required for recognition and endocytosis of yeasts. In contrast, using PMA-induced differentiated THP-1, we observed that the presence of TLR2 was required for efficient uptake and endocytosis of both C. albicans and S. cerevisiae. TLR2 and galectin-3, which are expressed at the level of phagosomes containing C. albicans, were shown to be associated in differentiated macrophages after incubation with this sole species. These data suggest that macrophages differently sense C. albicans and S. cerevisiae through a mechanism involving TLR2 and galectin-3, which probably associate for binding of ligands expressing -1,2 mannosides specific to the C. albicans cell wall surface.

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 in part by the European Community Feder Fund, Program Interreg IIIA. M.M.-E. was supported by the "Fundación Séneca", Murcia, Spain.

² Address correspondence and reprint requests to Dr. Thierry Jouault, Institut National de la Santé et de la Recherche Médicale, Unité 799, Laboratoire de Mycologie Fondamentale et Appliquée, Université de Lille II, Faculté de Médecine H. Warembourg, Pôle Recherche, Place Verdun, 59037 Lille, France. E-mail address: tjouault{at}univ-lille2.fr

³ Abbreviations used in this paper: PRM, pathogen-recognition molecule; PAMP, pathogen-associated molecular pattern; PLM, phospholipomannan; KO, knockout; WT, wild type; DC-SIGN, dendritic cell-specific ICAM-3 grabbing nonintegrin; SIGNR1, a murine homolog of human DC-SIGN.

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