Abstract
Mucosal tissues are the predominant sites for genital HIV-1 transmission. We investigated the mechanisms by which broadly neutralizing antibodies (bNAbs) inhibit HIV-1 replication in a coculture model including primary mucosal dendritic cells (DCs), such as Langerhans cells, interstitial dendritic cells, and CD4(+) T lymphocytes. We show that bNAbs efficiently prevent HIV-1 infection by inhibiting HIV-1 transmission to CD4(+) T lymphocytes. This inhibition of cell-to-cell transmission was observed with equal potency as the inhibition of cell-free infection of primary CD4(+) T lymphocytes. In addition, a decrease in HIV-1 replication in DCs and the induction of DC maturation were detected. This additional inhibition was Fc mediated as it was blocked by the use of specific anti-FcγR monoclonal Abs. The DC maturation by bNAbs during HIV transmission may contribute to mucosal protection. Therefore, multiple antibody-mediated inhibitory functions should be combined for the improvement of future preventive/therapeutic strategies to cure HIV.
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