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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 Î²-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 Î²-glucan, the loss of galectin-3 dramatically accentuates the failure to trigger an appropriate TNF-Î± response.