Low levels of productive HIV infection in Langerhans cell-like dendritic cells differentiated in the presence of TGF-beta 1 and increased viral replication with CD40 ligand-induced maturation

Langerhans cells (LC) represent dendritic cells (DC) within mucosal epithel ium that are purported initial targets for HIV following sexual exposure to virus. Here, morphologic, phenotypic, functional and HIV infection experim ents were performed using monocyte-derived DC cultured in the presence of G M-CSF, IL-4 and TGF-beta1 (G4T-DC), GM-CSF and IL-4 (G4-DC), and G4T-DC inc ubated for an additional 3 days with CD40 ligand (CD40L-DC). G4T-DC, which demonstrated characteristics of immature LC, could be productively infected by either R5- or X4-HIV strains. Infection levels, however, were markedly lower than those observed in immature G4-DC. Surprisingly, CD40L-DC, which demonstrated features of mature LC, could be productively infected with HIV at higher levels than immature G4T-DC. Productive HIV infection in these t hree DC populations correlated positively with cell surface expression of C D4, CCR5 and CXCR4. We suggest that low levels of HIV infection in LC-like G4T-DC indicate an inefficient mechanism by which HIV can initially infect individuals, perhaps explaining the relative difficulty in becoming infecte d during sexual exposure to virus. In addition, enhanced HIV infection in L C-like G4T-DC following CD40L treatment suggests a mechanism by which infla mmatory CD40L(+) T cells, if present in mucosal tissue, could lead to incre ased HIV transmission rates.