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Fungal recognition is mediated by the association of dectin-1 and galectin-3 in macrophages

Esteban, Alexandre, Popp, Maximilian W., Vyas, Valmik K., Strijbis, Karin, Ploegh, Hidde L., Fink, Gerald R.
Proceedings of the National Academy of Sciences of the United States of America 2011 v.108 no.34 pp. 14270-14275
Candida albicans, beta-glucans, fungi, immune response, leukocytes, macrophages, transmembrane proteins, tumor necrosis factor-alpha
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.