Background: There are currently 37 million individuals living with HIV (human immunodeficiency virus), and no clinically approved vaccine. At mucosal sites of initial virus infection, type I interferons (IFNs) such as IFN-α and IFN-β represent a potent first line of innate immunity, and are produced by a subset of dendritic cells (DCs) called plasmacytoid dendritic cells (pDCs). Although HIV successfully inhibits IFN-β induction in its various target cells including myeloid DCs and CD4+ T cells, IFN-α/β production by pDCs is thought to compensate for this block, limiting initial viral replication. However, the early dynamics between HIV and pDCs at mucosal sites, and their role in enhancing or reducing HIV infection, remains poorly understood.
Aims: This study aims to characterise the initial interactions of human primary pDCs on HIV-infected monocyte-derived dendritic cells and sorted memory CD4+ T cells using in vitro cocultures, to determine the effect of IFN production by pDCs on HIV spread and transfer.
Results: HIV-infected primary DCs and resting memory CD4+ T cells induced IFN production by pDCs, resulting in reduced HIV spread in DCs. This effect was diminished upon treatment with blocking antibodies to IFNα, IFNβ and IFNαβ receptor. However, HIV spread was increased in a subset-specific manner in CD4+ T cells upon pDC cocultures, particularly in transitional and effector memory subsets. The observed changes in HIV infection correlated with increased expression of DC and T cell activation markers respectively. Further experiments to determine the effect of pDCs on HIV transfer from DCs to CD4+ T cells will be performed, with the view to translate results from these model cells to clinically relevant human mucosal tissue samples.