HIV-1 Replication in Langerhans and Interstitial Dendritic Cells Is Inhibited by Neutralizing and Fc-Mediated

Langerhans cells (LCs) and interstitial dendritic cells (IDCs) may be among the first human immunode-ficiency virus type 1 (HIV-1) targets after sexual transmission. We generated cells of these types by differen-tiation of purified CD34 cord blood cells. After in vitro infection with R5-tropic strains, we obtained similar percentages of infected cells for both dendritic cell (DC) subsets. Moreover, LC infection was not increased by blockage of langerin by antilangerin. These results indicate that, under our experimental conditions, there was no evidence of any preference of HIV replication in LCs versus IDCs. The inhibitory activity of HIV-1-specific IgAs and IgGs against HIV-1 replication in LCs and IDCs was analyzed. We found that neutralizing antibodies inhibit HIV-1 infection of both DC subsets. Interestingly, HIV-1 was inhibited more efficiently by the IgGs than the corresponding IgA, due to an Fc receptor-dependent mechanism. Moreover, nonneutralizing inhibitory IgGs were able to inhibit infection of both LCs and IDCs. These results underline the importance of HIV-1 inhibition by the binding of the Fc part of IgGs to Fc receptors and suggest that the induction of neutralizing and nonneutralizing inhibitory IgGs in addition to neutralizing IgAs at mucosal sites may contribute to protection against sexual transmission of HIV-1. Currently, sexual transmission is the major route of new human immunodeficiency virus type 1 (HIV-1) infection. On