Model for local skin defense against dengue virus infection

Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN/CD209) was recently identified as a molecule that facilitates Dengue virus entry, leading to productive cellular infection. Initially, DC-SIGN expression was thought to be restricted to dendritic cells, however, it is now known that tissue macrophages also express it. Here we review a paper that used an ex vivo and an in vitro model of skin-dwelling macrophages expressing DC-SIGN, demonstrating that they are nonproductively infected with the Dengue virus. The authors reveal a novel type I interferon-independent mechanism whereby the virus enters these DC-SIGN-bearing cells but traffics to poorly acidified phagosomes, thereby limiting viral replication. We discuss this new model to study early infection and local host defenses against viral replication using IL-10-derived dermal macrophages expressing DC-SIGN.