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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3846. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by van Kooten, C. Search for Related Content PubMed Articles by van Kooten, C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Comment on Herre et al, page 4038 Dectin-1: unique appetite for yeast Cees van Kooten LEIDEN UNIVERSITY MEDICAL CENTER Dectin-1 is a myeloid receptor involved in phagocytosis of fungal pathogens that uses a unique mechanism of internalization and cellular signaling. Phagocytosis of pathogens is a critically important activity of cells of the innate immune system. Professional phagocytes, such as macrophages, are equipped with a wide array of cell surface receptors, which are either directly or indirectly involved in recognition, uptake, and presentation of these antigens, as well as cellular signaling. The indirect receptors, such as Fc receptor (FcR) and complement receptors, are well characterized and recognize pathogens opsonized with immunoglobulins and active complement fragments.1 Signaling via FcRis especially well established and involves the associated common gamma chain, which bears an immunoreceptor tyrosine-based activation motif (ITAM) critical for this activity. In addition, professional phagocytes/antigen-presenting cells express direct pattern recognition receptors, many belonging to the C-type lectin family, including macrophage mannose receptor (CD206) and scavenger receptor, but also receptors specific for dendritic cell subsets such as DC-SIGN (CD209), Langerin (CD207), DEC-205 (CD205), and BDCA2.2 Dectin-1 is another receptor broadly expressed on myeloid cells belonging to this family that recognizes -glucan structures, such as those exposed on the outside of fungal pathogens.3 Interestingly, this receptor combines the extracellular lectin domain with an intracellular region reminiscent of an ITAM motif. A study by Herre and colleagues in this issue of Blood further unravels the intracellular mechanisms of Dectin-1-mediated phagocytosis. Using transfected 3T3 fibroblasts, the critical contribution of the ITAM motif was demonstrated. Intracellular truncation or point mutation in the membrane proximal tyrosine residue did not affect binding, but hampered phagocytosis of yeast particles. The use of pharmacologic inhibitors also suggested that Dectin-1-mediated and FcR-mediated signaling followed a similar process. However, major differences were found when studies were performed in either RAW macrophages, transduced with the Dectin-1 receptor, or freshly isolated macrophages. For FcR signaling, the Syk kinase is a pivotal component,4 as confirmed by the authors showing the inability of macrophages from Syk-/- mice to take up opsonized sheep red blood cells. However, the same cells were fully competent in Dectin-1-mediated internalization (see figure). Herre et al went one step further and investigated whether the intracellular trafficking of the Dectin-1 receptor was affected by the nature of the ligand. The uptake of large particles was associated with a re-expression of the receptor completely dependent of de novo protein synthesis. However, smaller -glucans, such as laminarin, showed a receptor recycling independent of protein synthesis. It is conceivable that this difference has major implications for the antigen-presentation process and deserves further attention. Moreover it will be interesting to study these processes in the different myeloid cells expressing Dectin-1. Finally, the results of Herre et al raise the question of whether other cellular processes initiated by Dectin-1 triggering, such as production of inflammatory mediators, are also determined by the nature of the recognized ligand. Comparison of Dectin-1 and FcR-mediated phagocytosis in macrophages, demonstrating that Dectin-1-mediated phagocytosis is Syk-independent.   References Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol. 1999;17: 593-623.[CrossRef][Medline] [Order article via Infotrieve] Geijtenbeek TB, van Vliet SJ, Engering A, 't Hart BA, van Kooyk Y. Self- and nonself-recognition by C-type lectins on dendritic cells. Annu Rev Immunol. 2004;22: 33-54.[CrossRef][Medline] [Order article via Infotrieve] Brown GD, Gordon S. Immune recognition: a new receptor for beta-glucans. Nature. 2001;413: 36-37.[Medline] [Order article via Infotrieve] Turner M, Schweighoffer E, Colucci F, Di Santo JP, Tybulewicz VL. Tyrosine kinase SYK: essential functions for immunoreceptor signalling. Immunol Today. 2000;21: 148-154.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: 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 Blood 2004 104: 4038-4045. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by van Kooten, C. Search for Related Content PubMed Articles by van Kooten, C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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