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

Mucosal Immunol. 2017 Mar;10(2):531-544. doi: 10.1038/mi.2016.72. Epub 2016 Aug 31.

Abstract

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 CD11blow 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CD11c Antigen / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • Elafin / metabolism
  • Estradiol / pharmacology
  • Female
  • Genitalia, Female / immunology*
  • HIV / immunology*
  • HIV / pathogenicity
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • Humans
  • Immunity, Innate*
  • Interleukin-8 / metabolism
  • Lectins, C-Type / metabolism
  • Lipopolysaccharide Receptors / metabolism
  • Phagocytosis
  • Receptors, CCR5 / metabolism
  • Receptors, Cell Surface / metabolism
  • Secretory Leukocyte Peptidase Inhibitor / metabolism

Substances

  • CCR5 protein, human
  • CD11c Antigen
  • Cell Adhesion Molecules
  • Chemokine CCL2
  • DC-specific ICAM-3 grabbing nonintegrin
  • Elafin
  • Interleukin-8
  • Lectins, C-Type
  • Lipopolysaccharide Receptors
  • Receptors, CCR5
  • Receptors, Cell Surface
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • Estradiol