Placental expression of DC-SIGN may mediate intrauterine vertical transmission of HIV.

Abstract

Mechanisms of transplacental transmission of human immunodeficiency virus (HIV) are poorly understood. DC-SIGN is a C-type lectin able to bind HIV gp120 with high affinity, mediating HIV adsorption to the surface of dendritic cells for up to several days. Via this mechanism, DC-SIGN significantly enhances the infection of CD4(+) co-receptor (CCR5 or CXCR4)(+) T lymphocytes in trans. In this study, DC-SIGN-specific serum was developed to investigate the cell type responsible for the high level of DC-SIGN RNA expression previously observed in the placenta. DC-SIGN expression was shown on CD68(+) HLA-II(+) CD14(low) S100(+/-) CD83(-) CD86(-) cmrf-44(-) villous cells consistent with Hofbauer cells and also on CD68(+) HLA-II(+) CD14(high) S100(-) CD83(-) CD86(-) cmrf-44(-) decidual macrophages. The DC-SIGN(+) Hofbauer cells co-express CD4 and the chemokine receptors, CCR5 and CXCR4, observations which may account for the ability of these cells to become infected with HIV. These fetal DC-SIGN(+) cells are separated by only a layer of trophoblast from both DC-SIGN(+) maternal cells and maternal blood, potential sources of HIV in infected mothers. Previous studies have suggested that this trophoblast layer is frequently breached during pregnancy. It is therefore proposed that DC-SIGN may facilitate the transplacental transmission of HIV.