Immune recognition of Candida albicans beta-glucan by dectin-1.
Beta (1,3)-glucans represent 40% of the cell wall of the yeast Candida albicans. The dectin-1 lectin-like receptor has shown to recognize fungal beta (1,3)-glucans and induce innate immune responses. The importance of beta-glucan-dectin-1 pathways for the recognition of C. albicans by human primary blood cells has not been firmly established. In this study we demonstrate that cytokine production by both human peripheral blood mononuclear cells and murine macrophages is dependent on the recognition of beta-glucans by dectin-1. Heat killing of C. albicans resulted in exposure of beta-glucans on the surface of the cell wall and subsequent recognition by dectin-1, whereas live yeasts stimulated monocytes mainly via recognition of cell-surface mannans. Dectin-1 induced cytokine production through the following 2 pathways: Syk-dependent production of the T-helper (Th) 2-type anti-inflammatory cytokine interleukin-10 and Toll-like receptor-Myd88-dependent stimulation of monocyte-derived proinflammatory cytokines, such as tumor necrosis factor-alpha . In contrast, stimulation of Th1-type cytokines, such as interferon-gamma , by C. albicans was independent of the recognition of beta-glucans by dectin-1. In conclusion, C. albicans induces production of monocyte-derived and T cell-derived cytokines through distinct pathways dependent on or independent of dectin-1.
Gow
Neil A R
NA
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom. m.gow@abdn.ac.uk
Netea
Mihai G
MG
Munro
Carol A
CA
Ferwerda
Gerben
G
Bates
Steven
S
Mora-Montes
Héctor M
HM
Walker
Louise
L
Jansen
Trees
T
Jacobs
Liesbeth
L
Tsoni
Vicky
V
Brown
Gordon D
GD
Odds
Frank C
FC
Van der Meer
Jos W M
JW
Brown
Alistair J P
AJ
Kullberg
Bart Jan
BJ
D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D006801:Humans; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D000099181:Dectin-1
D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000099181:Dectin-1; C045268:beta-glucan receptor