Constitutive and induced expression of DC-SIGN on dendritic cell and macrophage subpopulations in situ and in vitro

Abstract

DC-SIGN is a C-type lectin, highly expressed on the surface of immature dendritic cells (DCs), that mediates efficient infection of T cells in trans by its ability to bind HIV-1, HIV-2, and SIV. In addition, the ability of DC-SIGN to bind adhesion molecules on surfaces of naïve T cells and endothelium also suggests its involvement in T-cell activation and DC trafficking. To gain further insights into the range of expression and potential functions of DC-SIGN, we performed a detailed analysis of DC-SIGN expression in adult and fetal tissues and also analyzed its regulated expression on cultured DCs and macrophages. First, we show that DC-SIGN expression is restricted to subsets of immature DCs in tissues and on specialized macrophages in the placenta and lung. There were no overt differences between DC-SIGN expression in adult and fetal tissues except that DC-SIGN expression in alveolar macrophages was only present after birth. Similarly, in tissues, DC-SIGN was observed primarily on immature (CD83-negative) DCs. Secondly, in the peripheral blood, we found expression of DC-SIGN on a small subset of BDCA-2+ plasmacytoid DC precursors (pDC2), concordant with our finding of large numbers of DC-SIGN-positive cells in allergic nasal polyps (previously shown to be infiltrated by DC2). Triple-label confocal microscopy indicated that DC-SIGN was colocalized with BDCA-2 and CD123 on DCs in nasal polyp tissue. Consistent with this finding is our observation that DC-SIGN can be up-regulated on monocyte-derived macrophages upon exposure to the Th2 cytokine, IL-13. In summary, our data demonstrate the relevant populations of DC and macrophages that express DC-SIGN in vivo where it may impact the efficiency of virus infection and indicate that DC-SIGN expression may be involved in the Th2 axis of immunity.