ABSTRACT
Langerhans cells (LC) are thought to be the only mononuclear phagocyte population in the epidermis where they detect pathogens. Here, we show that CD11c+ dendritic cells (DCs) are also present. These cells are transcriptionally similar to dermal cDC2 but are more efficient antigen-presenting cells. Compared to LCs, epidermal CD11c+ DCs are enriched in anogenital tissues where they preferentially interact with HIV, express the higher levels of HIV entry receptor CCR5, support the higher levels of HIV uptake and replication and are more efficient at transmitting the virus to CD4 T cells. Importantly, these findings are observed using both a lab-adapted and transmitted/founder strain of HIV. We also describe a CD33low cell population, which is transcriptionally similar to LCs but does not appear to function as antigen-presenting cells or acts as HIV target cells. Our findings reveal that epidermal DCs in anogenital tissues potentially play a key role in sexual transmission of HIV.
Subject(s)
Dendritic Cells/virology , Epidermal Cells/virology , HIV Infections/transmission , HIV-1/immunology , Antigen Presentation/immunology , CD11c Antigen/metabolism , Cells, Cultured , Dendritic Cells/immunology , Dendritic Cells/metabolism , Epidermal Cells/immunology , Epidermal Cells/metabolism , Epidermis/immunology , Female , HIV Infections/immunology , HIV Infections/virology , HIV-1/pathogenicity , Healthy Volunteers , Humans , Male , Primary Cell Culture , Receptors, CCR5/metabolism , Sialic Acid Binding Ig-like Lectin 3/metabolism , T-Lymphocytes/immunology , Virus InternalizationABSTRACT
Mononuclear phagocytes are present in skin and mucosa and represent one of the first lines of defense against invading pathogens, which they detect via an array of pathogen-binding receptors expressed on their surface. However, their extraction from tissue is difficult, and the isolation technique used has functional consequences on the cells obtained. Here, we compare mononuclear phagocytes isolated from human skin using either enzymatic digestion or spontaneous migration. Cells isolated via enzymatic digestion are in an immature state, and all subsets are easily defined. However, cells isolated by spontaneous migration are in a mature state, and CD141 cross-presenting DCs (cDC1) are more difficult to define. Different pathogen-binding receptors are susceptible to cleavage by blends of collagenase, demonstrating that great care must be taken in choosing the correct enzyme blend to digest tissue if carrying out pathogen-interaction assays. Finally, we have optimized mononuclear phagocyte culture conditions to enhance their survival after liberation from the tissue.
