Specific recognition of Candida albicans by macrophages requires galectin-3 to discriminate Saccharomyces cerevisiae and needs association with TLR2 for signaling.
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 beta-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 beta-1,2 mannosides specific to the C. albicans cell wall surface.
Jouault
Thierry
T
INSERM Unité 799 and Laboratoire Fondamentale et Appliquée, Université de Lille II, Faculté de Médecine H. Warembourg, Pôle Recherche, Place Verdun, 59037 Lille, France. tjouault@univ-lille2.fr
El Abed-El Behi
Miryam
M
Martínez-Esparza
María
M
Breuilh
Laetitia
L
Trinel
Pierre-André
PA
Chamaillard
Mathias
M
Trottein
Francois
F
Poulain
Daniel
D
D000818:Animals; D015153:Blotting, Western; D002176:Candida albicans / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005656:Fungal Proteins / Q000276:immunology; D037502:Galectin 3 / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*
D005656:Fungal Proteins; D037502:Galectin 3; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2