title: Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages.
abstract: Dectin-1, the major β-glucan receptor in leukocytes, triggers an effective immune response upon fungal recognition. Here we use sortase-mediated transpeptidation, a technique that allows placement of a variety of probes on a polypeptide backbone, to monitor the behavior of labeled functional dectin-1 in live cells with and without fungal challenge. Installation of probes on dectin-1 by sortagging permitted highly specific visualization of functional protein on the cell surface and its subsequent internalization upon ligand presentation. Retrieval of sortagged dectin-1 expressed in macrophages uncovered a unique interaction between dectin-1 and galectin-3 that functions in the proinflammatory response of macrophages to pathogenic fungi. When macrophages expressing dectin-1 are exposed to Candida albicans mutants with increased exposure of β-glucan, the loss of galectin-3 dramatically accentuates the failure to trigger an appropriate TNF-α response.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Esteban
authors.forename: Maximilian W
authors.initials: MW
authors.lastname: Popp
authors.forename: Valmik K
authors.initials: VK
authors.lastname: Vyas
authors.forename: Karin
authors.initials: K
authors.lastname: Strijbis
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Fink
mesh_terms: D000818:Animals; D019921:Biotinylation; D001854:Bone Marrow Cells / Q000166:cytology; D002176:Candida albicans / Q000502:physiology*; D004705:Endocytosis / Q000187:drug effects; D037502:Galectin 3 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D037181:Lectins, C-Type; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D015335:Molecular Probes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D013194:Staining and Labeling; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan / Q000378:metabolism; D047071:beta-Glucans / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D037502:Galectin 3; D037181:Lectins, C-Type; D008565:Membrane Proteins; D015335:Molecular Probes; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D047071:beta-Glucans; D000099181:Dectin-1