Dendritic Cells (DCs) present in the anogenital mucosa are one of the first cells to encounter HIV during sexual intercourse. They play a crucial role in transmission as they efficiently pass the virus onto T cells. DCs bind HIV via C-type lectin receptors (CLR) expressed on their surface, which results in either uptake via endocytosis, or transfer to CD4/CCR5 resulting in productive infection. Corresponding to the two routes of entry, HIV can be efficiently transferred to T cells in two successive phases; an early first phase associated with CLR mediated uptake which probably occurs within the mucosa; and a late second phase associated with CD4/CCR5 mediated productive infection which probably occurs after migration to lymph nodes.
The anogenital mucosa is made up of various tissues which contain a variety of DCs subsets. Each subset expresses unique combinations of CLRs which affect the way they interact with HIV and the efficiency by which they can mediate its transfer to T cells. Although there is some knowledge about the way epidermal DCs (Langerhans cells) interact with HIV via their CLR langerin, very little is known about the way DCs in the dermis and lamina propria interact with the virus. This is particularly the case in the anorectal mucosa which represents a critical gap in our knowledge as transmission rates via anal intercourse are up to 100 times higher than vaginal intercourse.
Here we present data comparing the ways in which all the known DC subsets found within human sexual mucosal tissue interact with HIV. We have examined the efficiency by which they can mediate transfer to T cells. Critically we show that some DC subsets are far more efficient than others at mediating transfer and that only certain subsets are able to mediate both phases of transfer.