Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production.
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.
Underhill
David M
DM
Institute for Systems Biology, Seattle, WA 98103, USA. dunderhill@systemsbiology.org
Rossnagle
Eddie
E
Lowell
Clifford A
CA
Simmons
Randi M
RM
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism; D012756:Sheep; D015398:Signal Transduction; D019809:Streptavidin / Q000494:pharmacology; D000072377:Syk Kinase; D014162:Transfection; D000099181:Dectin-1
D016207:Cytokines; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011505:Protein-Tyrosine Kinases; D017382:Reactive Oxygen Species; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D019809:Streptavidin; D000072377:Syk Kinase; D000099181:Dectin-1; C000606896:SYK protein, human; C000606897:Syk protein, mouse