Dendritic cells and HIV transmission: roles and subsets of antigen-presenting cells in the human anogenital tract

Dendritic cells (DCs) are potent antigen-presenting cells and play a key role in facilitating the sexual transmission of HIV, functioning as a delivery system responsible for trafficking the virus from exposed barrier sites to their key target cells, CD4 T cells. Although the role of DCs in HIV transmission is well established, the recent advent of high-parameter, single-cell detection technologies, coupled with improved cell isolation techniques, has led to the rapid reclassification of the DC landscape, particularly within human barrier tissues. The identification of new subsets introduces the challenge of incorporating previously understood transmission principles with new, cell-specific, functional nuances to identify the key DCs responsible for facilitating HIV infection. This review explores the history of research linking DCs with HIV transmission as well as our understanding of how HIV manipulates DC biology to achieve this purpose. Furthermore, it provides an up-to-date understanding of the antigen-presenting cell landscape within human anogenital tissues and how each subset contributes to sexual transmission. Uncovering the cells and biological processes responsible for the sexual transmission of HIV is a fundamental step in the pursuit of an HIV vaccine and better prophylaxis to block infection.