AM3 modulates dendritic cell pathogen recognition capabilities by targeting DC-SIGN

Diego Serrano-Gómez, Rocío T. Martínez-Nunez, Elena Sierra-Filardi, Nuria Izquierdo, María Colmenares, Jesus Pla, Luis Rivas, Javier Martinez-Picado, Jesús Jimenez-Barbero, José Luis Alonso-Lebrero, Salvador González, Angel L. Corbí

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    8 Citations (Scopus)

    Abstract

    AM3 (Inmunoferon) is an orally effective immunomodulator that influences the regulatory and effector functions of the immune system whose molecular mechanisms of action are mostly unknown. We hypothesized that the polysaccharide moiety of AM3 (IF-S) might affect immune responses by modulating the lectin-dependent pathogen recognition abilities of human dendritic cells. IF-S inhibited binding of viral, fungal, and parasite pathogens by human monocyte-derived dendritic cells in a dose-dependent manner. IF-S specifically impaired the pathogen recognition capabilities of DC-SIGN, as it reduced the attachment of Candida, Aspergillus, and Leishmania to DC-SIGN transfectants. IF-S also inhibited the interaction of DC-SIGN with both its cellular counterreceptor (intercellular adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120 protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV trans-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN internalization in DCs without affecting mannose receptor expression, and 1D saturation transfer difference nuclear magnetic resonance demonstrated that IF-S directly interacts with DC-SIGN on the cell surface. Therefore, the polysaccharide moiety of AM3 directly influences pathogen recognition by dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is the target for an immunomodulator and imply that the adjuvant and immunomodulatory actions of AM3 are mediated, at least in part, by alteration of the DC-SIGN functional activities. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
    Original languageEnglish
    Pages (from-to)2313-2323
    JournalAntimicrobial Agents and Chemotherapy
    Volume51
    Issue number7
    DOIs
    Publication statusPublished - 1 Jul 2007

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