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.
References
[1]
Alangaden GJ (2011) Nosocomial fungal infections: epidemiology, infection control, and prevention. Infect Dis Clin North Am 25: 201–225.
[2]
Chen LY, Liao SY, Kuo SC, Chen SJ, Chen YY, et al. (2011) Changes in the incidence of candidaemia during 2000–2008 in a tertiary medical centre in northern Taiwan. J Hosp Infect 78: 50–53.
[3]
Skrzypek F, Cenci E, Pietrella D, Rachini A, Bistoni F, et al. (2009) Dectin-1 is required for human dendritic cells to initiate immune response to Candida albicans through Syk activation. Microbes Infect 11: 661–670.
[4]
Kennedy AD, Willment JA, Dorward DW, Williams DL, Brown GD, et al. (2007) Dectin-1 promotes fungicidal activity of human neutrophils. Eur J Immunol 37: 467–478.
[5]
Brouwer N, Dolman KM, van Houdt M, Sta M, Roos D, et al. (2008) Mannose-binding lectin (MBL) facilitates opsonophagocytosis of yeasts but not of bacteria despite MBL binding. J Immunol 180: 4124–4132.
[6]
Sealy PI, Garner B, Swiatlo E, Chapman SW, Cleary JD (2008) The interaction of mannose binding lectin (MBL) with mannose containing glycopeptides and the resultant potential impact on invasive fungal infection. Med Mycol 46: 531–539.
[7]
Ghiran I, Barbashov SF, Klickstein LB, Tas SW, Jensenius JC, et al. (2000) Complement receptor 1/CD35 is a receptor for mannan-binding lectin. J Exp Med 192: 1797–1808.
[8]
McGreal E, Gasque P (2002) Structure-function studies of the receptors for complement C1q. Biochem Soc Trans 30: 1010–1014.
[9]
Brown GD, Gordon S (2001) Immune recognition. A new receptor for beta-glucans. Nature 413: 36–37.
[10]
Goodridge HS, Reyes CN, Becker CA, Katsumoto TR, Ma J, et al. (2011) Activation of the innate immune receptor Dectin-1 upon formation of a ‘phagocytic synapse’. Nature 472: 471–475.
[11]
Drummond RA, Brown GD (2011) The role of Dectin-1 in the host defence against fungal infections. Curr Opin Microbiol 14: 392–399.
[12]
Gantner BN, Simmons RM, Underhill DM (2005) Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J 24: 1277–1286.
[13]
Linden JR, Maccani MA, Laforce-Nesbitt SS, Bliss JM (2010) High efficiency opsonin-independent phagocytosis of Candida parapsilosis by human neutrophils. Med Mycol 48: 355–364.
[14]
Sa？d-Sadier N, Padilla E, Langsley G, Ojcius DM (2010) Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS One 5: e10008.
[15]
Kerrigan AM, Brown GD (2011) Syk-coupled C-type lectins in immunity. Trends Immunol 32: 151–156.
[16]
Ghiran I, Barbashov SF, Klickstein LB, Tas SW, Jensenius JC, et al. (2000) Complement receptor 1/CD35 is a receptor for mannan-binding lectin. J Exp Med 192: 1797–1808.
[17]
van Asbeck EC, Hoepelman AI, Scharringa J, Herpers BL, Verhoef J (2008) Mannose binding lectin plays a crucial role in innate immunity against yeast by enhanced complement activation and enhanced uptake of polymorphonuclear cells. BMC Microbiol 8: 229–238.
[18]
Lillegard JB, Sim RB, Thorkildson P, Gates MA, Kozel TR (2006) Recognition of Candida albicans by mannan-binding lectin in vitro and in vivo. J Infect Dis 193: 1589–1597.
[19]
Han X, Yu R, Zhen D, Tao S, Schmidt M, et al. (2011) β-1,3-Glucan-induced host phospholipase D activation is involved in Aspergillus fumigatus internalization into type II human pneumocyte A549 cells. PLoS One 2011: e21468.
[20]
Yang Z, Marshall JS (2009) Zymosan treatment of mouse mast cells enhances Dectin-1 expression and induces Dectin-1-dependent reactive oxygen species (ROS) generation.
[21]
Sa？d-Sadier N, Padilla E, Langsley G, Ojcius DM (2010) Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS One 5: e10008.
