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.
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.
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
Janet A
JA
Willment
Hsi-Hsien
HH
Lin
Delyth M
DM
Reid
Philip R
PR
Taylor
David L
DL
Williams
Simon Y C
SY
Wong
Siamon
S
Gordon
Gordon D
GD
Brown
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation / Q000276:immunology*; D004338:Drug Combinations; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000502:physiology*; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology*; D015054:Zymosan / Q000378:metabolism; D000099181:Dectin-1
D000276:Adjuvants, Immunologic; D003907:Dexamethasone; D004338:Drug Combinations; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007166:Immunosuppressive Agents; D016753:Interleukin-10; D018793:Interleukin-13; D015847:Interleukin-4; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015054:Zymosan; D000099181:Dectin-1