Phagocytosis of Fungal Agents and Yeast Via Macrophage Cell Surface Scavenger Receptors

BackgroundMacrophages mediate phagocytosis via cell-surface pattern-recognition-receptors (PRRs) known to recognize certain fixed patterns on pathogens. Of these PRRs, scavenger receptors class A I and II (SR-A I and II) are known to mediate the binding and internalization of a large variety of Gram +ve and Gram –ve bacteria. Their role in phagocytic clearance of fungal agents has not been described.MethodsFluorescence microscopy and phagocytosis assays were used on murine macrophage cell lines RAW264.7. Chinese hamster ovarian cell lines (CHO) transfected with SR-A-I or SRA-II and known ligands that block SRA-uptake were used to test the ability of these cells to bind fungal agents. Macrophages from mice genetically deficient in SRA (MSR-knockouts) were used to establish whether absence of these receptors affects fungal uptake.ResultsWe show for the first time that the SR-A I and II on macrophages are involved in both the binding and phagocytosis of S. cerevisiae and Candida albicans. SRA-mediated binding and internalization of these pathogens is specifically inhibited by known ligands of SRA (Fucoidan and Poly G) in a dose-titratable manner. Further, CHO cells transfected with either SR-A-I or SRA-II show an increased ability to bind and internalize S. cerevisiae compared with the non-transfected parental cells. In contrast, the macrophages that are deficient in the scavenger receptor (obtained from MSR–/– mice) do not show a decreased ability to phagocytose fungal agents.ConclusionsScavenger receptors mediate phagocytosis of fungal agents, representing perhaps an alternative, fall back mechanism.