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The effect of a mannose binding protein on macrophage interactions with Candida albicans
D J Kitz1, P D Stahl, J R Little
1Department of Biological Sciences, Southern Illinois University, Edwardsville 62026-1651.
Abstract:
A soluble mannose binding protein (MBP), obtained from rabbit serum, was found to inhibit phagocytosis of Candida albicans by bone marrow derived, cultured murine macrophages. During in vitro incubation of yeast with lymphocyte-free macrophage populations uptake of the yeast was significantly reduced at MBP concentrations of 5 micrograms/ml. A similar reduction in yeast phagocytosis was produced by dextrose, d-fucose, l-fucose, d-mannose and alpha-methyl-d-mannoside but required saccharide concentrations of 25-50 mg/ml. Inhibition of phagocytosis of the yeast also resulted from pretreatment of either the macrophages or the yeasts with MBP followed by washing. As expected, the addition of mannan to the assay medium blocked the inhibitory effect of MBP for uptake of C. albicans. These findings suggest that both cell bound and soluble mannose receptors may be important modulators of macrophage-Candida interactions.
Insights
Soluble mannose-binding protein (MBP) inhibits Candida albicans phagocytosis by macrophages. This suggests mannose receptors play a key role in macrophage-fungal interactions.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Phagocytosis is a critical immune mechanism by which macrophages engulf and eliminate pathogens like Candida albicans.
- Mannose-binding protein (MBP) is a key component of the innate immune system involved in pathogen recognition.
- Macrophage receptors are crucial for mediating interactions with microbial pathogens.
Purpose of the Study:
- To investigate the role of soluble mannose-binding protein (MBP) in the phagocytosis of Candida albicans by murine macrophages.
- To explore the involvement of mannose receptors in the interaction between macrophages and Candida albicans.
Main Methods:
- In vitro incubation of Candida albicans with bone marrow-derived murine macrophages.
- Assessment of yeast uptake in the presence of varying concentrations of soluble mannose-binding protein (MBP) and specific saccharides.
- Pretreatment experiments involving MBP and yeast or macrophages, followed by washing.
- Inhibition assays using mannan to block MBP activity.
Main Results:
- Soluble mannose-binding protein (MBP) significantly inhibited the phagocytosis of Candida albicans by macrophages at concentrations as low as 5 µg/ml.
- Other saccharides like dextrose, d-fucose, l-fucose, d-mannose, and α-methyl-d-mannoside also reduced yeast phagocytosis but required higher concentrations (25-50 mg/ml).
- Pre-treating either macrophages or yeast with MBP before washing also inhibited phagocytosis, indicating MBP's direct role.
- Mannan addition blocked the inhibitory effect of MBP, confirming MBP's mechanism of action.
Conclusions:
- Soluble mannose-binding protein (MBP) is a potent inhibitor of Candida albicans phagocytosis by macrophages.
- These findings highlight the significant role of both soluble and cell-bound mannose receptors in modulating macrophage interactions with Candida albicans.
- Understanding these interactions is crucial for developing targeted immunotherapies against fungal infections.