PMID- 27579858 OWN - NLM STAT- MEDLINE DCOM- 20171107 LR - 20230203 IS - 1935-3456 (Electronic) IS - 1933-0219 (Print) IS - 1933-0219 (Linking) VI - 10 IP - 2 DP - 2017 Mar TI - Dendritic cells from the human female reproductive tract rapidly capture and respond to HIV. PG - 531-544 LID - 10.1038/mi.2016.72 [doi] AB - 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 approximately 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-alpha2 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. FAU - Rodriguez-Garcia, M AU - Rodriguez-Garcia M AD - Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA. FAU - Shen, Z AU - Shen Z AD - Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA. FAU - Barr, F D AU - Barr FD AD - Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA. FAU - Boesch, A W AU - Boesch AW AD - Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA. FAU - Ackerman, M E AU - Ackerman ME AD - Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA. FAU - Kappes, J C AU - Kappes JC AD - Department of Medicine and UAB Center for AIDS Research, University of Alabama at Birmingham, Research Service Birmingham, Birmingham, Alabama, USA. AD - Birmingham Veterans Affairs Medical Center, Research Service Birmingham, Birmingham, Alabama, USA. FAU - Ochsenbauer, C AU - Ochsenbauer C AD - Department of Medicine and UAB Center for AIDS Research, University of Alabama at Birmingham, Research Service Birmingham, Birmingham, Alabama, USA. FAU - Wira, C R AU - Wira CR AD - Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA. LA - eng GR - T32 CA073479/CA/NCI NIH HHS/United States GR - P30 AI027767/AI/NIAID NIH HHS/United States GR - R01 AI102838/AI/NIAID NIH HHS/United States GR - P30 CA023108/CA/NCI NIH HHS/United States GR - R01 AI117739/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20160831 PL - United States TA - Mucosal Immunol JT - Mucosal immunology JID - 101299742 RN - 0 (CCR5 protein, human) RN - 0 (CD11c Antigen) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokine CCL2) RN - 0 (DC-specific ICAM-3 grabbing nonintegrin) RN - 0 (Elafin) RN - 0 (Interleukin-8) RN - 0 (Lectins, C-Type) RN - 0 (Lipopolysaccharide Receptors) RN - 0 (Receptors, CCR5) RN - 0 (Receptors, Cell Surface) RN - 0 (SLPI protein, human) RN - 0 (Secretory Leukocyte Peptidase Inhibitor) RN - 4TI98Z838E (Estradiol) SB - IM MH - CD11c Antigen/metabolism MH - Cell Adhesion Molecules/metabolism MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Dendritic Cells/*immunology/virology MH - Elafin/metabolism MH - Estradiol/pharmacology MH - Female MH - Genitalia, Female/*immunology MH - HIV/*immunology/pathogenicity MH - HIV Infections/*immunology/transmission MH - Humans MH - *Immunity, Innate MH - Interleukin-8/metabolism MH - Lectins, C-Type/metabolism MH - Lipopolysaccharide Receptors/metabolism MH - Phagocytosis MH - Receptors, CCR5/metabolism MH - Receptors, Cell Surface/metabolism MH - Secretory Leukocyte Peptidase Inhibitor/metabolism PMC - PMC5332537 MID - NIHMS805792 COIS- Disclosure. The authors declared no conflict of interest. EDAT- 2016/09/01 06:00 MHDA- 2017/11/08 06:00 PMCR- 2017/03/06 CRDT- 2016/09/01 06:00 PHST- 2016/01/07 00:00 [received] PHST- 2016/07/07 00:00 [accepted] PHST- 2016/09/01 06:00 [pubmed] PHST- 2017/11/08 06:00 [medline] PHST- 2016/09/01 06:00 [entrez] PHST- 2017/03/06 00:00 [pmc-release] AID - S1933-0219(22)00664-X [pii] AID - 10.1038/mi.2016.72 [doi] PST - ppublish SO - Mucosal Immunol. 2017 Mar;10(2):531-544. doi: 10.1038/mi.2016.72. Epub 2016 Aug 31.