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

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

Author information

1
Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
2
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
3
Department of Medicine and UAB Center for AIDS Research, University of Alabama at Birmingham, Research Service Birmingham, Birmingham, Alabama, USA.
4
Birmingham Veterans Affairs Medical Center, Research Service Birmingham, Birmingham, Alabama, USA.

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.

PMID:
27579858
PMCID:
PMC5332537
DOI:
10.1038/mi.2016.72
[Indexed for MEDLINE]
Free PMC Article

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