Dendritic cells from the human female reproductive tract rapidly capture and respond to HIV

Dendritic cells (DCs) throughout the female reproductive tract (FRT) were examined for phenotype, HIV capture ability and innate anti-HIV responses. Two main CD11c⁺ DC subsets were identified: CD11b⁺ and CD11b^low DCs. CD11b⁺CD14⁺ DCs were the most abundant throughout the tract. A majority of CD11c⁺CD14⁺ cells corresponded to CD1c⁺ myeloid DCs, whereas the rest lacked CD1c and CD163 expression (macrophage marker) and may represent monocyte-derived cells. In addition, we identified CD103⁺ DCs, located exclusively in the endometrium, whereas DC-SIGN⁺ DCs were broadly distributed throughout the FRT. Following exposure to GFP-labeled HIV particles, CD14⁺ DC-SIGN⁺ as well as CD14⁺ DC-SIGN^- cells captured virus, with ∼30% of these cells representing CD1c⁺ myeloid DCs. CD103⁺ DCs lacked HIV capture ability. Exposure of FRT DCs to HIV induced secretion of CCL2, CCR5 ligands, interleukin (IL)-8, elafin, and secretory leukocyte peptidase inhibitor (SLPI) within 3 h of exposure, whereas classical pro-inflammatory molecules did not change and interferon-α2 and IL-10 were undetectable. Furthermore, elafin and SLPI upregulation, but not CCL5, were suppressed by estradiol pre-treatment. Our results suggest that specific DC subsets in the FRT have the potential for capture and dissemination of HIV, exert antiviral responses and likely contribute to the recruitment of HIV-target cells through the secretion of innate immune molecules.