Dendritic-cell interactions with HIV: infection and viral dissemination

Key Points Dendritic cells (DCs) are located in the mucosae and the lymphoid tissues. They are proposed to be among the first cells to encounter HIV during sexual transmission. The main populations of DCs include myeloid DCs and plasmacytoid DCs in the blood, and Langerhans cells in the tissues. Myeloid DCs, plasmacytoid DCs and Langerhans cells are all susceptible to infection with HIV; they can also transfer HIV to CD4 + T cells. Follicular DCs can trap and maintain large quantities of HIV, thereby functioning as a persistent reservoir of virus. Immunomodulation of DCs by HIV infection is a key aspect of viral pathogenesis, particularly through the modulation or interference of the antigen-presenting function of DCs. DCs express high levels of C-type lectins, including DC-specific intercellular adhesion molecule 3 (ICAM3)-grabbing non-integrin (DC-SIGN; also known as CD209). C-type lectins are the main HIV attachment factors at the surface of dermal and mucosal DCs. DCs have DC-SIGN-dependent and DC-SIGN-independent mechanisms of HIV trans -infection of CD4 + T cells. The efficiency of HIV transmission can be increased by maturation of DCs. The transfer of virus from DCs to CD4 + T cells occurs in three discrete steps. First, DCs capture and bind HIV. Second, HIV traffics within these DCs. And third, HIV is transferred to CD4 + T cells by a process that is known as trans -infection. DC-mediated HIV trans -infection might occur by several distinct processes that can take place concurrently, including rapid HIV trans -infection through infectious synapses and exosome-associated viruses. HIV transmission can also be mediated by de novo viral production in DCs, known as cis -infection. Elucidating the interactions of HIV with DCs will be vital to uncover the contribution of DCs to viral pathogenesis. HIV has evolved ways to exploit dendritic cells to facilitate spread of the virus through the body. Dendritic cells can mediate the transfer of HIV to target CD4 + T cells through several distinct mechanisms, as discussed in this Review. Dendritic cells (DCs) are crucial for the generation and the regulation of adaptive immunity. Because DCs have a pivotal role in marshalling immune responses, HIV has evolved ways to exploit DCs, thereby facilitating viral dissemination and allowing evasion of antiviral immunity. Defining the mechanisms that underlie cell–cell transmission of HIV and understanding the role of DCs in this process should help us in the fight again