Up-regulation of CCR5 expression in the placenta is associated with human immunodeficiency virus-1 vertical transmission

The role of placenta in vertical transmission is not yet fully understood A protective role of the placenta during gestation is suggested by the findi ng that caesarian sections reduce the risk of transmission of human immunod eficiency virus (HIV)-1 from mother to child three- to fourfold. Here we in vestigated whether the immunological milieu of the placenta might be import ant in HIV-1 transmission. In situ imaging of immunohistochemically stained placenta sections and reverse transcriptase-polymerase chain reaction demo nstrated a fourfold increase in CCR5:CXCR4 expression ratio in placentae fr om transmitting women compared to placentae from nontransmitting women This chemokine receptor repertoire was consistent with an up-regulation of inte rleukin-4 and interleukin-10 expression in placentae from nontransmitting p lacentae compared to transmitting placentae lit situ imaging demonstrated t hat CCR5 and CXCR4 were expressed on placental macrophages and lymphocytes but not in trophoblasts. Simultaneous immunofluorescence/ultrasensitive in situ hybridization for HIV-1 gag-pol mRNA. revealed that HIV-1 infects prim arily CXCR4-expressing cells in placentae from nontransmitting women wherea s predominantly CCR5-expressing cells were infected in placentae from trans mitting women. These data are consistent with transmission of a homogeneous population of nonsyncytium-inducing HIV-1 isolates that use CCR5 as co-rec eptor.