Cell wall mannoprotein of Candida albicans polarizes macrophages and affects proliferation and apoptosis through activation of the Akt signal pathway

Candida albicans is a commensal fungus that associates with human hosts. Under normal circumstances this interaction does not produce any severe life-threatening disease, as macrophages of the innate immune system will result in its clearance. However, disorders may arise in immunosuppressed individuals. To understand the bioactivity of Candida albicans cell wall polysaccharides, which represent an important component of its function, mannoprotein from this fungus was extracted, purified and analyzed. Mannoprotein with alpha-(1,2) and alpha-(1,6) linkages was investigated with use of HPLC and NMR. Co-incubation of mannoprotein with macrophages resulted in a mannoprotein with the potential to polarize macrophages to M1 and promote phagocytosis/microbial killing ability thus increasing the clearance of pathogens through Akt2. Moreover, mannoprotein within the cell wall promoted cell proliferation and inhibited apoptosis by activation of the Akt signaling pathway. Collectively, alpha-(1,6)(1,2)-mannoprotein, one of the five polysaccharides extracted from the cell wall of Candida albicans, demonstrates immune-enhancing effects by activation of the Akt signaling pathway. These findings provide important new insights into the biological effects of polysaccharides on macrophages. Such information can then serve as the foundation for the development of novel anti-fungal medications.