P16.08
Background: The mucosal tissues contain various HIV target cells including antigen-presenting cells (APCs) such as Langerhans cells (LCs), interstitial dendritic cells (iDCs) or plasmacytoid (pDCs) in addition to CD4 T lymphocytes. These APCs play a major role in HIV-1 dissemination. Broadly neutralizing antibodies (bNAbs) need to impair HIV-1 cell-to-cell transmission to efficiently protect from HIV-1 transmission at the mucosal site. The aim of this study is to decipher the mechanisms by which Abs protect from HIV-1 transfer.
Methods: We used a physiologically relevant model of primary APCs, infected with R5 HIV-1 isolates or transmitted/founder virus, cocultivated with autologous CD4 T cells in the presence or absence of bNAbs. At 48 and 72h post-infection, the percentages of infected cells, the expression of intracellular SAMHD1 and CD83+/CD86+ maturation markers were determined by flow cytometry. IFN-α production was measured in the culture supernatant.
Results: We found that APCs efficiently transferred HIV-1 to adjacent CD4 T cells. Interestingly, coculture with CD4 T cells downregulated SAMHD1 expression in DCs, enhanced HIV-1 replication, induced DC maturation and increased IFN-α secretion. bNAbs efficiently prevented HIV-1 transfer to CD4 T cells with a similar efficiency as cell-free infection. Moreover, DC maturation and IFN-α production were modulated by Abs. For example, bNAb VRC01 did not impair DC maturation and IFN-α secretion, whereas 4E10 increased immune cell activation. This Ab-associated modulation of APC activation participates to the overall Ab inhibition of HIV-1 transmission.
Conclusions: During HIV cell-to-cell transmission, crosstalk between APCs and autologous CD4 T lymphocytes occurs leading to increased HIV replication, immune activation and immune sensing. HIV-1-specific Abs modulate these immune functions, therefore interfering with HIV-1 transmission. Consequently, this additional Ab function should be taken into consideration for the design of new vaccine strategies.
