Langerhans Cells (LCs) were previously thought to be the sole, HIV-transmitting, mononuclear phagocyte present within both the skin epidermis and genital stratified squamous epithelium (SSE). In 2019, our lab demonstrated that these compartments also contain dendritic cells (epi-DCs). Interestingly, we have shown that epi-DCs are not only more efficient at facilitating HIV infection compared to LCs but are also highly enriched within the SSE tissues associated with the sexual transmission of the virus. Invited talks by Dr. Bertram and Prof. Harman will provide a functional analysis of epi-DCs.
Here, we used a combination of immunofluorescent microscopy and fluorescence-activated cell sorting/cytometry on surgically removed skin and mucosal tissues to establish a migration marker for these cells. This discovery suggests that epi-DCs are not technically epithelial resident cells. Rather, DCs from the underlying tissues can cross the tightly packed basement membrane into the SSE – a significant discovery for dermal immunology.
We then utilised the discovery of this migration marker to quantify DC migration in response to HIV. Using multiplex immunofluorescence microscopy, we were able to observe, in situ, that topical HIV application to the epithelial surface drove the migration of DCs into the SSE and closer to the virus. Furthermore, we showed that HIV’s interactions with the SSE’s surface caused the DCs in the underlying tissues to localise closer to the basement membrane – again migrating towards the virus.
In essence, we have demonstrated that epi-DCs are highly efficient HIV-facilitating, antigen-presenting cells enriched within genital SSE. Our findings indicate that these DCs are not only migratory but also chemoattracted to HIV in situ. Therefore, we are currently attempting to identify the migratory molecules responsible for this chemotaxis towards the epithelial surface. If we can determine what causes these cells to move towards HIV, we can explore ways to block this process.