The induction of inflammation by dectin-1 in vivo is dependent on myeloid cell programming and the progression of phagocytosis.
Dectin-1 is the archetypal signaling, non-Toll-like pattern recognition receptor that plays a protective role in immune defense to Candida albicans as the major leukocyte receptor for beta-glucans. Dectin-1-deficiency is associated with impaired recruitment of inflammatory leukocytes and inflammatory mediator production at the site of infection. In this study, we have used mice to define the mechanisms that regulate the dectin-1-mediated inflammatory responses. Myeloid cell activation by dectin-1 is controlled by inherent cellular programming, with distinct macrophage and dendritic cell populations responding differentially to the engagement of this receptor. The inflammatory response is further modulated by the progression of the phagocytosis, with "frustrated phagocytosis" resulting in dramatically augmented inflammatory responses. These studies demonstrate that dectin-1 in isolation is sufficient to drive a potent inflammatory response in a context-dependent manner. This has implications for the mechanism by which myeloid cells are activated during fungal infections and the processes involved in the therapeutic manipulation of the immune system via exogenous dectin-1 stimulation or blockade.
Rosas
Marcela
M
Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, United Kingdom.
Liddiard
Kate
K
Kimberg
Matti
M
Faro-Trindade
Inês
I
McDonald
Jacqueline U
JU
Williams
David L
DL
Brown
Gordon D
GD
Taylor
Philip R
PR
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D003713:Dendritic Cells; D007249:Inflammation / Q000209:etiology*; D037181:Lectins, C-Type; D008264:Macrophages; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009181:Mycoses / Q000276:immunology; D022423:Myeloid Cells / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D010587:Phagocytosis; D047071:beta-Glucans / Q000276:immunology; D000099181:Dectin-1
D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D047071:beta-Glucans; D000099181:Dectin-1