HIV-1 border patrols: Langerhans cells control antiviral responses and viral transmission

Langerhans cells (LCs) reside in the mucosal epithelia and are refractory to HIV-1 infection; HIV-1 capture by C-type lectin receptor langerin and subsequent targeting to Birbeck granules prevents infection. Furthermore, LCs restrict transmission of CXCR4-using HIV-1 variants, which underscores the role of immature LCs as gatekeepers in the selection of HIV-1 variants. Interaction of langerin on LCs with hyaluronic acid on dendritic cells facilitates cross-presentation of HIV-1 to CD8(+) T cells. Activation of LCs upon inflammation bypasses the langerin-dependent barrier, which favors cross-presentation and increases susceptibility of LCs to HIV-1 infection. These recent developments not only highlight the plasticity of LCs but also define an important role for LC-dendritic cell crosstalk at the periphery in directing adaptive immune responses to viruses.