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Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin mediates binding and internalization of Aspergillus fumigatus conidia by dendritic cells and macrophages.

Diego Serrano-Gómez·Angeles Domínguez-Soto·Julio Ancochea·José A Jimenez-Heffernan·Juan Antonio Leal·Angel L Corbí
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Abstract

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.

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Antigens, CDAspergillus fumigatusBinding SitesBinding, CompetitiveCell Adhesion MoleculesCell DifferentiationCells, CulturedDendritic CellsGalactoseHumansK562 CellsLectins, C-TypeLungMacrophages, AlveolarMannansMonocytesReceptors, Cell SurfaceSpores, FungalJournal ArticleResearch Support, Non-U.S. Gov't

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Diego Serrano-Gómez, Angeles Domínguez-Soto, Julio Ancochea, José A Jimenez-Heffernan, Juan Antonio Leal, Angel L Corbí. 2004-11-01. Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin mediates binding and internalization of Aspergillus fumigatus conidia by dendritic cells and macrophages.. https://doi.org/10.4049/jimmunol.173.9.5635

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