Defining the role of human anogenital antigen-presenting cells in HIV transmission — ASN Events
  1. Schedule
  2. Parallel Symposium C: DCs in Infection & Host Defense
  3. Defining the role of human anogenital antigen-presenting cells in HIV transmission

Defining the role of human anogenital antigen-presenting cells in HIV transmission (139740)

Andrew N Harman 1 2 , Daniel J Buffa 1 2 , Kirstie M Bertram 1 2 , Erica E Vine 1 3 , Thomas R O'Neil 1 3 , Anthony L Cunningham 1 2
  1. Westmead Millennium Institute, Westmead, NSW, Australia
  2. University of Sydney, Westmead, NEW SOUTH WALES, Australia
  3. University of Sydney, Sydney, NSW, A

Antigen presenting cells play a critical role in HIV transmission as they capture the virus in the anogenital mucosa and then deliver it to CD4 T cells, the primary HIV target cells. We have defined the APCs that inhabit every human anogenital tissue and identified 3 key HIV transmitting subsets, which are all dendritic cells (DC). Firstly, epithelial DCs (epi-DC) which we were the first to report and secondly, CD207+ DC2 and monocyte derived DC (MDDC) in the underlying lamina propria.

Here we will firstly summarize our discovery of epi-DCs and show that they: i) are highly enriched in human anogenital epithelium; ii) play a preferential role in HIV transmission over Langerhans cells; iii) are highly potent at stimulating CD4 and CD8 T cells.  

Secondly, we will report our in situ findings using RNAscope and spatial proteomics to define the dynamics of HIV transmission in rectal tissue. We show that HIV preferentially localizes with DC2 within 2 hours of tissue exposure which then rapidly cluster with CD4 T cells in the lamina propria (not lymphoid tissue) allowing for transfer of HIV. CD207+ DC2 also traffic the virus to lymphoid follicles which form a conduit to the sub-mucosa where the virus is taken up by specific macrophage subsets.