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The Journal of Immunology, 2004, 172: 1157-1162.
Copyright © 2004 by The American Association of Immunologists

The Role of SIGNR1 and the {beta}-Glucan Receptor (Dectin-1) in the Nonopsonic Recognition of Yeast by Specific Macrophages1

Philip R. Taylor2,*, Gordon D. Brown*, Jurgen Herre*, David L. Williams{dagger}, Janet A. Willment* and Siamon Gordon*

* Sir William Dunn School of Pathology, Oxford University, South Parks Road, Oxford, United Kingdom; and {dagger} Department of Surgery, James H. Quillen College of Medicine, Johnson City, TN 37614

We recently demonstrated that the {beta}-glucan receptor Dectin-1 ({beta}GR) was the major nonopsonic {beta}-glucan receptor on macrophages (M{phi}) for the yeast-derived particle zymosan. However, on resident peritoneal M{phi}, we identified an additional mannan-inhibitable receptor for zymosan that was distinct from the M{phi} mannose receptor (MR). In this study, we have studied the mannose-binding potential of murine M{phi} and identified the dendritic cell-specific ICAM-3-grabbing nonintegrin homolog, SIGN-related 1 (SIGNR1), as a major MR on murine resident peritoneal M{phi}. Both SIGNR1 and {beta}GR cooperated in the nonopsonic recognition of zymosan by these M{phi}. When SIGNR1 was introduced into NIH3T3 fibroblasts or RAW 264.7 M{phi}, it conferred marked zymosan-binding potential on these cells. However, in the nonprofessional phagocytes (NIH3T3), SIGNR1 was found to be poorly phagocytic, suggesting that other receptors such as {beta}GR may play a more dominant role in particle internalization on professional phagocytes. Binding of zymosan to RAW 264.7 M{phi} expressing SIGNR1 resulted in TNF-{alpha} production. Treatment of RAW 264.7 M{phi} expressing SIGNR1, which express low levels of {beta}GR, with {beta}-glucans had little effect on binding or TNF-{alpha} production, indicating that there was no absolute requirement for {beta}GR in this process. These studies have identified SIGNR1 as a major MR for fungal and other pathogens present on specific subsets of M{phi}.




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