Expression of the HIV-1 co-receptors CCR5 and CXCR4 on placental macrophages and the effect of IL-10 on their expression

Abstract

The chemokine receptors CCR5 and CXCR4 play a key role in HIV-1 infection as co-receptors for viral entry. In the placenta, an important natural barrier to HIV, the expression and regulation of these receptors has yet to be elucidated. In this study, we determined the expression of CCR5 and CXCR4 co-receptors on placental macrophages (PM) and the effect of interleukin-10 (IL-10) on co-receptor expression. PM were isolated from term placentae of HIV-uninfected mothers and cultured for up to 11 days. The cells were stimulated with IL-10 for 24 h and stained with specific antibodies to CCR5, CXCR4, CD4, CD3, CD11c and CD14 for flow cytometry. Unstimulated PM expressed significantly more CCR5 than CXCR4. Expression of both co-receptors was upregulated by stimulation with IL-10 at 24 h post-stimulation. In vivo expression of these co-receptors from frozen sections revealed a higher percentage of CCR5 positive cells. This is the first study in which expression of both co-receptors is detected on the PM membrane. These results are consistent with previous studies performed in our laboratory where PM were readily infected by CCR5-using HIV strains but could not be productively infected by HIV strains that exclusively use CXCR4 as a co-receptor.