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

HIV attachment, trafficking and transmission in human dendritic cells

Dendritic cells (DC) provide a bridge between the innate and acquired immune system. HIV exploits the complex pathways of microbial antigen uptake and transport by these cells for initial entry and dissemination. Over the past few years the binding of gp120 to the C type lectin DC-SIGN on transfected cells and dendritic cells has been investigated and proposed as the major receptor for HIV binding on (all) DCs. However in this thesis the C type lectin receptors (CLRs), langerin, uniquely expressed on Langerhans cells (LC), and mannose receptor (MR) shown to be expressed on dermal DC subsets were also demonstrated to bind HIV gp120 through its mannose saccharides in addition to DC-SIGN