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The placenta is a fetal organ constituting the interface between the foetus and maternal tissue. It is locked in a constant battle between immune tolerance of the allogenic foetus and immunological functionality to protect it from in-utero infection. Placental macrophages, or Hofbauer cells (HBC), are present from 18 days gestation and are the only detectable placental immune cell for the majority of gestation. They sit on the foetal side of the single-cellular syncytiotrophoblast layer separating maternal and foetal blood and putatively play an integral role in setting the immune environment of the placenta. HBC express CD4, CCR5, CXCR4, and other HIV-implicated molecules like DC-SIGN and Siglec-1, suggesting that they might facilitate in-utero HIV infection. Through collaborations with Manu Vatish at Oxford we are characterising HBC from both HIV-unexposed and HIV-exposed sex-discordant twins. The project led by Oliver Sampson also includes collaborations with William James at Oxford to use human-induced pluripotent stem cells as a model of tissue-resident macrophages to investigate the role of sex-hormones in modulating HBC functionality and to utilise CRISPR/Cas9 to assess the involvement of sex-related genes. Better understanding of the route of in-utero HIV transmission will inform strategies to protect babies from mother-to-child transmission during pregnancy, especially in settings like South Africa where sustained ART adherence is problematic.