Abstract
Dectin-1 is a lectin receptor for beta-glucan that is important for innate macrophage recognition of fungi and contributes to phagocytosis, reactive oxygen production, and induction of inflammatory cytokines. The mechanisms by which Dectin-1 mediates intracellular signaling are just beginning to be defined. Spleen tyrosine kinase (Syk) is a protein tyrosine kinase that is critical for adaptive immune responses where it mediates signaling through B-cell receptors, T-cell receptors, and Fc receptors. Here we report that Dectin-1 activates Syk in macrophages and is important for Dectin-1-stimulated reactive oxygen production, but not for phagocytosis. Syk activation is restricted to a subpopulation of macrophages that is in equilibrium with cells that cannot activate the pathway. The proportion of macrophages using this signaling pathway can be modulated by cytokine treatment. Thus, Dectin-1 signaling reveals dynamic macrophage heterogeneity in inflammatory activation potential.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Cell Line
-
Cytokines / metabolism
-
Enzyme Activation
-
Enzyme Precursors / metabolism*
-
Erythrocytes / metabolism
-
Flow Cytometry
-
Humans
-
Inflammation
-
Intracellular Signaling Peptides and Proteins
-
Lectins, C-Type
-
Macrophages / metabolism*
-
Membrane Proteins / metabolism
-
Membrane Proteins / physiology*
-
Mice
-
Microscopy, Fluorescence
-
Nerve Tissue Proteins / metabolism
-
Nerve Tissue Proteins / physiology*
-
Phagocytosis
-
Protein-Tyrosine Kinases / metabolism*
-
Reactive Oxygen Species*
-
Receptors, Antigen, B-Cell / metabolism
-
Receptors, Antigen, T-Cell / metabolism
-
Receptors, Fc / metabolism
-
Sheep
-
Signal Transduction
-
Streptavidin / pharmacology
-
Syk Kinase
-
Transfection
Substances
-
Cytokines
-
Enzyme Precursors
-
Intracellular Signaling Peptides and Proteins
-
Lectins, C-Type
-
Membrane Proteins
-
Nerve Tissue Proteins
-
Reactive Oxygen Species
-
Receptors, Antigen, B-Cell
-
Receptors, Antigen, T-Cell
-
Receptors, Fc
-
dectin 1
-
Streptavidin
-
Protein-Tyrosine Kinases
-
SYK protein, human
-
Syk Kinase
-
Syk protein, mouse