Dendritic Cell-Specific Intercellular Adhesion Molecule 3-Grabbing Nonintegrin Mediates Binding and Internalization of Aspergillus fumigatus Conidia by Dendritic Cells and Macrophages

摘要

Aspergillus fumigatus is responsible for a large percentage of nosocomial opportunistic fungal infections in immunocompromised hosts,especially during cytotoxic chemotherapy and after bone marrow transplantation,and is currently a major direct cause of death in leukemia patients.Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is a type II C-type lectin that functions as an adhesion receptor and is used by viral and bacterial pathogens to gain access to human DC.We report that DC-SIGN specifically interacts with clinical isolates of A.fumigatus.DC-SIGN-dependent binding of A.fumigatus conidia can be demonstrated with stable transfectants and monocyte-derived DC and is inhibited by anti-DC-SIGN Abs.Binding and internalization of A.fumigatus conidia correlates with DC-SIGN cell surface expression levels and is abolished in the presence of A.funigatus-derived cell wall galactomannans.The clinical relevance of this interaction is emphasized by the presence of DC-SIGN in lung DC and alveolar macrophages,and further illustrated by the DC-SIGN-dependent attachment of A.fumigatus conidia to the cell membrane of IL-4-treated monocyte-derived macrophages.Our results suggest the involvement of DC-SIGN in the initial stages of pulmonary infection as well as in fungal spreading during invasive aspergillosis.