Manipulation of Mononuclear Phagocytes by HIV: Implications for Early Transmission Events.

Mononuclear phagocytes are antigen presenting cells that play a key role in linking the innate and adaptive immune systems. In tissue, these consist of Langerhans cells, dendritic cells and macrophages, all of which express the key HIV entry receptors CD4 and CCR5 making them directly infectible with HIV. Mononuclear phagocytes are the first cells of the immune system to interact with invading pathogens such as HIV. Each cell type expresses a specific repertoire of pathogen binding receptors which triggers pathogen uptake and the release of innate immune cytokines. Langerhans cells and dendritic cells migrate to lymph nodes and present antigens to CD4 T cells, whereas macrophages remain tissue resident. Here we review how HIV-1 manipulates these cells by blocking their ability to produce innate immune cytokines and taking advantage of their antigen presenting cell function in order to gain transport to its primary target cells, CD4 T cells.

Human Dendritic Cell Subsets, Ontogeny, and Impact on HIV Infection.

Dendritic cells (DCs) play important roles in orchestrating host immunity against invading pathogens, representing one of the first responders to infection by mucosal invaders. From their discovery by Ralph Steinman in the 1970s followed shortly after with descriptions of their in vivo diversity and distribution by Derek Hart, we are still continuing to progressively elucidate the spectrum of DCs present in various anatomical compartments. With the power of high-dimensional approaches such as single-cell sequencing and multiparameter cytometry, recent studies have shed new light on the identities and functions of DC subtypes. Notable examples include the reclassification of plasmacytoid DCs as purely interferon-producing cells and re-evaluation of intestinal conventional DCs and macrophages as derived from monocyte precursors. Collectively, these observations have changed how we view these cells not only in steady-state immunity but also during disease and infection. In this review, we will discuss the current landscape of DCs and their ontogeny, and how this influences our understanding of their roles during HIV infection.