The interaction of HIV with dendritic cells: outcomes and pathways

Abstract

Dendritic cells (DCs), including Langerhans Cells (LCs), are probably among the earliest targets of HIV infection. Their localization in mucosal epithelia and in the T cell areas of lymphoid organs, as well as their crucial role in capturing antigens and initiating T cell responses, highlight their potential importance. Studies with cells in culture have addressed different outcomes of the HIV--DC interaction, which include: direct productive infection of DC; carriage of virus by DC to CD4+ T cells; transfer of virus between DC and T cells at an infectious synapse; and immune evasion strategies of infected DC. Here we review the literature covering these areas, including current knowledge of underlying mechanisms or pathways.

Figure 1

Model of HIV mucosal transmission. Vaginal epithelium is composed of a stratified multicellular squamous epithelium, whereas cervical and rectal mucosae have a single-layer cellular lining. During and after crossing the mucosal epithelia, HIV infects LCs, DCs and macrophages, as well as mucosal CD4⁺ T lymphocytes, in the mucosal and sub-epithelial level. Alternatively, DCs (and potentially LCs) capture virus without being infected and transfer it in trans across an infectious synapse to CD4⁺ T cells. The ‘founder’ infected cells amplify virus and migrate to the peripheral lymph nodes where they transfer virus to bystander cells. Viral load increases rapidly when the virus reaches the GALT.

Figure 2

The balance between resistance and infection of DC and LC subsets by HIV-1. (a) The C-type lectin, Langerin, on LCs has recently been reported to decrease infection of LCs, as well as transfer of HIV infection to CD4⁺ T cells. (b) The C-type lectin DC-SIGN (and probably other factors) increases HIV infection of DCs, as well as transfer of HIV infection to CD4⁺ T cells across an infectious synapse in trans. (c) Direct infection of DCs is limited by entry blocks linked to surface levels of CD4 and HIV co-receptors (CCR5), limited fusion of HIV with DCs, as well as cytoplasmic restriction factors APOBEC3G/3F. Post-integration blocks limit viral propagation from infected DCs.