Dendritic cells (DCs) and macrophages in the skin and mucosal surfaces are two of the first immune cell subsets to encounter vector-borne and sexually transmitted viruses. In the case of HIV and Herpes Simplex Virus, these cells play a direct role in their transmission. There are a number of different DC and macrophage subsets, which recognise and bind viruses via an array of cell-type specific pathogen binding receptors called C-type lectin receptors (CLRs). Virion binding to CLRs results in rapid endocytosis and subsequent antigen presentation on MHC class I and II.
We used multicolour flow cytometry to determine all the key DC and macrophage subsets in human skin and anogenital tissues, and to thoroughly characterise the full repertoire of CLRs and viral entry receptors that each subset expresses on their surface. Cells were either isolated via enzymatic digestion to liberate immature cells representative of the cells that encounter viruses at their portals of entry, or by allowing them to migrate out of the tissues to liberate cells more representative of those that have migrated to lymph nodes after virus capture.
We found that cells isolated by enzymatic digestion expressed much higher level of CLRs which were expressed in unique combinations of different cell subsets. Furthermore we found differences in CLR expression in cells derived from different anogenital tissues, especially between tissues lined with skin such as the labia and foreskin, and those consisting of mucosa such as the vagina and rectum. For example, we found significant differences in the expression of CLRs between different cell subsets that are known to bind HIV.
These differences in CLR expression profiles will determine which viruses can be detected and provides insight into which DC subsets mediate immunity against specific viral pathogens. This is useful for the development of mucosal vaccines.