However, HeLa cells derived from cervical carcinoma might not represent the best model to study the impact of promoter variants on DC-SIGN expression in macrophages. To address this issue, we further determine the net impact of susceptibilityassociated promoter mutations on DC-SIGN expression by measuring total DC-SIGN protein expression in Hofbauer cells. These cells are found within the chorionic villi beneath the syncytiotrophoblast layer at the maternal-fetal interface [33] . Term placentas contain a distinct population of Hofbauer cells that co-express DC-SIGN, CD163, CD14, CD68 and HLA-DR, a phenotype similar to alternatively activated macrophages (M2) known for their immunosuppressive properties [16, 33, 34] . Hofbauer cells were analysed by flow cytometry after isolation of mononuclear cells from term placentas of promoter WT p-336T/ p-201C and variants p-336C/p-201A carriers. CD14 + cells of high granularity that were negative for T, B and NK cell markers (CD3, CD19 and CD56) were identified as Hofbauer cells (CD14 + population) and two subsets of DC-SIGN + cells were observed (CD163 + and CD163 2 , Figure 2C ). CD163 + cells expressed significantly higher levels of DC-SIGN, HLA-DR and CD68 compared to CD163 2 cells ( Figure 2C ). We then compared levels of DC-SIGN expression in CD163 + and CD163 2 cells between infants carrying or not carrying promoter variants and born from HIV-1-negative or HIV-1-positive mothers ( Figure 2D ). In infants born to HIV-1-negative mothers, levels of DC-SIGN expression were reduced 1.9-fold (P = 0.0091) in CD163 + cells and 1.8-fold (P = 0.0305) in CD163 2 cells from infants carrying the promoter variants compared to infants harbouring the WT promoter sequence. Interestingly, DC-SIGN expression varied according to the mothers' HIV-1 status. In infants harbouring the WT sequence, levels of DC-SIGN expression were reduced 3.2-fold (P = 0.0402) by CD163 + cells and 2.2-fold (P = 0.0378) by CD163 2 cells in infants born from HIV-1-positive mothers compared to infants born from HIV-1-negative mothers. However, it remained unchanged in infants carrying the promoter variants. Hence, p-336C and p-201A altered DC-SIGN expression in placental Hofbauer cells and but their impact vary according maternal HIV-1 status.