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

Janet A Willment; Hsi-Hsien Lin; Delyth M Reid; Philip R Taylor; David L Williams; Simon Y C Wong; Siamon Gordon; Gordon D Brown

doi:10.4049/jimmunol.171.9.4569

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

J Immunol. 2003 Nov 1;171(9):4569-73. doi: 10.4049/jimmunol.171.9.4569.

Authors

Janet A Willment¹, Hsi-Hsien Lin, Delyth M Reid, Philip R Taylor, David L Williams, Simon Y C Wong, Siamon Gordon, Gordon D Brown

Affiliation

¹ Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.

PMID: 14568930
DOI: 10.4049/jimmunol.171.9.4569

Abstract

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 (Mphi). 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 Mphi-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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / pharmacology
Adjuvants, Immunologic / physiology
Animals
Dexamethasone / pharmacology*
Down-Regulation / immunology*
Drug Combinations
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
Immunosuppressive Agents / pharmacology
Interleukin-10 / physiology*
Interleukin-13 / pharmacology
Interleukin-4 / pharmacology
Lectins, C-Type
Lipopolysaccharides / pharmacology*
Macrophage Activation / drug effects
Macrophage Activation / immunology*
Macrophages, Peritoneal / drug effects
Macrophages, Peritoneal / immunology
Macrophages, Peritoneal / metabolism
Membrane Proteins / antagonists & inhibitors
Membrane Proteins / biosynthesis*
Membrane Proteins / physiology
Mice
Mice, Inbred BALB C
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / biosynthesis*
Nerve Tissue Proteins / physiology
Up-Regulation / immunology*
Zymosan / metabolism

Substances

Adjuvants, Immunologic
Drug Combinations
Immunosuppressive Agents
Interleukin-13
Lectins, C-Type
Lipopolysaccharides
Membrane Proteins
Nerve Tissue Proteins
dectin 1
Interleukin-10
Interleukin-4
Dexamethasone
Granulocyte-Macrophage Colony-Stimulating Factor
Zymosan