Distinct mechanisms of HIV transfer from macrophages or Langerhans dendritic cells to T lymphocytes

PERESSIN, M; PROUST, A; SCHMIDT, S; LAMBOTIN, M; SU, B; BIEDMA, M.E; LAUMOND, G; DECOVILLE, T; MOOG, C

Paris

Congreso; 30 Years of HIV science: Imagine the future; 2013

Objective: In addition to T cells, dendritic cells (DC) and macrophages residing at mucosal sites are considered as first HIV targetcells following sexual infection. Due to their antigen presenting cell (APCs) functions, DCs and macrophages are in close contactwith T cells, which favors efficient transfer of viral particles to lymphocytes, leading to rapid HIV-1 dissemination. In this study, weaim to understand the mechanisms and the respective contribution of DCs and macrophages in HIV transfer to T cells.Methods: Langerhans DCs and interstitial DCs (LCs/IDCs) were obtained by differentiation of CD34+ cord blood cells and MDMs(monocytes-derived macrophages) were differentiated from blood monocytes. LCs/IDCs or MDMs were incubated with HIV-1BaLduring 2 hours before extensive wash. These HIV-loaded APCs were then cocultivated with autologous stimulated CD4 T cells inpresence or absence of inhibitors. HIV infection was recorded 2 and 3 days post-infection by measurement of intracellular p24 ineach cell population and analyzed by flow cytometry.Results: We demonstrated that the mechanism of transfer from LCs/IDCs and MDMs to T cells differed in several points. First, thekinetic of HIV transfer to T cells was more rapid in MDMs, recorded within 48 hours versus 72 hours for LCs/IDCs. MDMs, that weremore susceptible to infection, transfer also HIV 4 fold more efficiently compared to DCs subsets. Moreover, trans-transfer(without de novo production of virus particles) was major in MDMs cocultures, compared to LCs/IDCs that mainly transfer HIV in cisto T cells. Finally, we demonstrated that the presence of T cells in the different APCs cocultures induced modifications of the fusionkinetic and influenced HIV infection cycle in APCs: increased replication in DCs subsets, and reduced in MDMs cocultures.Conclusion: Altogether, our results highlight the important contribution of each target cell population in HIV infection and transfer toT cells. Moreover, they emphasize the potential role of macrophages in HIV transmission to T lymphocytes at mucosal site.