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The Journal of Immunology, 2003, 171: 4569-4573.
Copyright © 2003 by The American Association of Immunologists

Dectin-1 Expression and Function Are Enhanced on Alternatively Activated and GM-CSF-Treated Macrophages and Are Negatively Regulated by IL-10, Dexamethasone, and Lipopolysaccharide 1

Janet A. Willment*, Hsi-Hsen Lin*, Delyth M. Reid{dagger}, Philip R. Taylor*, David L. Williams{ddagger}, Simon Y. C. Wong{dagger}, Siamon Gordon* and Gordon D. Brown2,*

* Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom; {dagger} Edward Jenner Institute for Vaccine Research, Compton, Berkshire, United Kingdom; and {ddagger} Department of Surgery, James H. Quillen College of Medicine, Johnson City, TN 37614

Dectin-1 is the major macrophage receptor for {beta}-glucans and generates a proinflammatory response through the recognition of these carbohydrates on fungal pathogens. We have examined the effects of cytokines and other agents on the expression and functions of dectin-1 in both resident and elicited murine peritoneal macrophages (M{phi}). Dectin-1 expression was found to be highly up-regulated by GM-CSF and by the cytokines that induce alternative macrophage activation, IL-4 and IL-13. In contrast, IL-10, LPS, and dexamethasone, but not IFN-{gamma}, down-regulated the expression of this receptor. Modulation of dectin-1 receptor levels correlated with the ability of these macrophages to bind zymosan and significantly affected the contribution of this receptor to the resultant proinflammatory response, as measured by the production of TNF-{alpha}, although some M{phi}-specific differences were observed. These results correlate with the known effects of these cytokines and other agents on the ability of the immune system to recognize and respond to fungal pathogens.


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