Abstract
Dendritic cells express lectins receptors, like DC-SIGN, which allow these cells to sense glycans that are present on various bacterial and viral pathogens. Interaction of DC-SIGN with carbohydrate moieties induces maturation of dendritic cells and promotes endocytosis of pathogens which is an important property of these professional antigen presenting cells. Uptake of pathogens by dendritic cells may lead to cross-presentation of antigens or infection of these cells, which ultimately results in activation of virus-specific T cells in draining lymph nodes. Little is known about the interaction of DC-SIGN with influenza A viruses. Here we show that a virus with a non-functional receptor binding site in its hemagglutinin, can replicate in cells expressing DC-SIGN. Also in the absence of sialic acids, which is the receptor for influenza A viruses, these viruses replicate in DC-SIGN expressing cells including human dendritic cells. Furthermore, the efficiency of DC-SIGN mediated infection is dependent on the extent of glycosylation of the viral hemagglutinin.
Highlights
DC-SIGN is a C-type lectin mainly present at the surface of dendritic cells (DC)
Were used to inoculate Madin-Darby Canine Kidney (MDCK) or MDCK DC-SIGN cells at a MOI of 0.01 and culture supernatants were collected at various time points post inoculation
In the present study we show that expression of DC-SIGN facilitates infection of cells by influenza A viruses independent of sialic acids, the natural receptor for these viruses, expressed on the target cell
Summary
DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin) is a C-type lectin mainly present at the surface of dendritic cells (DC). DC are antigen presenting cells that play a key role in the induction of the adaptive immune responses. They are able to present antigens to T cells and induce their maturation. DC-SIGN signalling modulates the status of DC, triggers their maturation and promotes the adaptive immune response [1]. For example ligands of DC-SIGN include bacteria and several viruses such as cytomegalovirus, Dengue virus, Ebola virus, hepatitis C virus, human immunodeficiency virus 1, SARS-coronavirus and West Nile virus [2,3,4,5,6,7,8,9,10]. Little is known about the interaction of DCSIGN with influenza A viruses
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