Phagocytosis of fungal agents and yeast via macrophage cell surface scavenger receptors.
BACKGROUND
Macrophages 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.


METHODS
Fluorescence 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.


RESULTS
We 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.


CONCLUSIONS
Scavenger receptors mediate phagocytosis of fungal agents, representing perhaps an alternative, fall back mechanism.
Wang
Ruibo
R
Division of Plastic Surgery, Department of Surgery and Center for Immunotherapy, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1601, USA.
Chandawarkar
Rajiv Y
RY
D000818:Animals; D016466:CHO Cells / Q000502:physiology; D002176:Candida albicans / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D016650:Fluorescein-5-isothiocyanate; D037181:Lectins, C-Type / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence / Q000379:methods; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000502:physiology; D051116:Receptors, Scavenger / Q000172:deficiency; D012441:Saccharomyces cerevisiae / Q000502:physiology; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000502:physiology*; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D016650:Fluorescein-5-isothiocyanate