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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4038-4045.
Prepublished online as a Blood First Edition Paper on August 10, 2004; DOI 10.1182/blood-2004-03-1140.
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IMMUNOBIOLOGY
Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages
Jurgen Herre,
Andrew S. J. Marshall,
Emmanuelle Caron,
Alexander D. Edwards,
David L. Williams,
Edina Schweighoffer,
Victor Tybulewicz,
Caetano Reis e Sousa,
Siamon Gordon, and
Gordon D. Brown
From the Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom; Centre for Molecular Microbiology and Infection and Department of Biological Sciences, Imperial College, London, United Kingdom; Immunobiology Laboratory, Cancer Research United Kingdom, London, United Kingdom; Department of Surgery, James H. Quillen College of Medicine, Johnson City, TN; National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom; and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch, South Africa.
The phagocytosis of pathogens is a critical event in host defense, not only for clearance of the invading microorganism, but also for the subsequent immune response. We have examined Dectin-1, a proinflammatory nonopsonic receptor for  -glucans, and show that it mediates the internalization of -glucan-bearing ligands, including yeast particles. Although requiring tyrosine phosphorylation and the cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM)-like motif, uptake mediated by Dectin-1 was different from any previously reported phagocytic receptor and was not dependent on Syk-kinase in macrophages. Furthermore, intracellular trafficking of this receptor was influenced by the nature of the -glucan ligand, which has significance for the biologic activity of these immunomodulatory carbohydrates. (Blood. 2004;104:4038-4045)
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