Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin mediates binding and internalization of Aspergillus fumigatus conidia by dendritic cells and macrophages.
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. fumigatus-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.
Serrano-Gómez
Diego
D
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Domínguez-Soto
Angeles
A
Ancochea
Julio
J
Jimenez-Heffernan
José A
JA
Leal
Juan Antonio
JA
Corbí
Angel L
AL
D015703:Antigens, CD / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D001665:Binding Sites / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D020014:K562 Cells; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008351:Mannans / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D013172:Spores, Fungal / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D037181:Lectins, C-Type; D008351:Mannans; D011956:Receptors, Cell Surface; C012990:galactomannan; D005690:Galactose