title: MBL-mediated opsonophagocytosis of Candida albicans by human neutrophils is coupled with intracellular Dectin-1-triggered ROS production.
abstract: Mannan-binding lectin (MBL), a lectin homologous to C1q, greatly facilitates C3/C4-mediated opsonophagocytosis of Candida albicans (C. albicans) by human neutrophils, and has the capacity to bind to CR1 (CD35) expressed on circulating neutrophils. The intracellular pool of neutrophil Dectin-1 plays a critical role in stimulating the reactive oxygen species (ROS) generation through recognition of β-1,3-glucan component of phagocytized zymosan or yeasts. However, little is known about whether MBL can mediate the opsonophagocytosis of Candida albicans by neutrophils independent of complement activation, and whether MBL-mediated opsonophagocytosis influence the intracellular expression of Dectin-1 and ROS production. Here we showed that the inhibited phagocytic efficiency of neutrophils as a result of blockage of Dectin-1 was compensated by exogenous MBL alone in a dose-dependent manner. Furthermore, the expressions of Dectin-1 at mRNA and intracellular protein levels were significantly up-regulated in neutrophils stimulated by MBL-pre-incubated C. albicans, while the expression of surface Dectin-1 remained almost unchanged. Nevertheless, the stimulated ROS production in neutrophils was partly and irreversibly inhibited by blockage of Dectin-1 in the presence of exogenous MBL. Confocal microscopy examination showed that intracellular Dectin-1 was recruited and co-distributed with ROS on the surface of some phagocytized yeasts. The β-1,3-glucanase digestion test further suggested that the specific recognition and binding site of human Dectin-1 is just the β-1,3-glucan moiety on the cell wall of C. albicans. These data demonstrate that MBL has an ability to mediate the opsonophagocytosis of Candida albicans by human neutrophils independent of complement activation, which is coupled with intracellular Dectin-1-triggered ROS production.
authors.affiliation: Center for Infectious Skin Diseases, Department of Dermatology, No.1 Hospital of Wuhan, Wuhan, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Li
authors.forename: Bilin
authors.initials: B
authors.lastname: Dong
authors.forename: Zhongsheng
authors.initials: Z
authors.lastname: Tong
authors.forename: Qinning
authors.initials: Q
authors.lastname: Wang
authors.forename: Weihuang
authors.initials: W
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jinbo
authors.initials: J
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Liuqing
authors.initials: L
authors.lastname: Chen
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Duan
mesh_terms: D002176:Candida albicans / Q000276:immunology / Q000472:pathogenicity; D002473:Cell Wall / Q000276:immunology / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000008:administration & dosage*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017463:Receptors, Complement 3b / Q000276:immunology / Q000378:metabolism; D015054:Zymosan / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D037601:Mannose-Binding Lectin; D017382:Reactive Oxygen Species; D017463:Receptors, Complement 3b; D015054:Zymosan; D047071:beta-Glucans; C546929:CLEC7A protein, human; D000099181:Dectin-1; C509991:CR1 protein, human; C033363:beta-1,3-glucan