Exposure of Macrophages to an Enzymatically Inactive Macrophage Mannose Receptor Ligand Augments KiIIing of Candida albicans

Abstract

Abstract

Macrophages (Mφ) are involved in host defenses against opportunistic pathogens. Previous studies by the present investigators indicate that Mφ exposed to enzymatically active myeloperoxidase (MPO), exhibited both increased phagocytosis and killing of Candida albicans. The purpose of this study was to determine if enzymatically inactive Mφ-mannose receptor (MMR) ligands could function similarly. Resident murine peritoneal Mφ were exposed to the MMR ligands, mannosylated bovine serum albumin (mBSA), and enzymatically inactive myeloperoxidase (iMPO), followed by exposure to opsonized C. albicans. Both mBSA and iMPO induced a slight increase in the number of phagocytizing cells; however, candidacidal activity was significantly higher in treated cultures compared to controls (P ≤ 0.001). The production of reactive oxygen intermediates (ROI) was detected using chemiluminescence. After employment of ROI scavengers, a decrease in candidacidal activity was observed. The data suggest that MMR-ligand interaction alone is sufficient to significantly enhance the candidacidal activity of Mφ via ROI, and that iMPO which is released at a site of inflammation induces Mφ-mediated killing of microorganisms. These findings indicate a previously unrecognized role of iMPO.