title: Dendritic cells from the human female reproductive tract rapidly capture and respond to HIV.
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 CD11blowDCs. 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.
authors: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors: M
authors: M
authors: Rodriguez-Garcia
authors: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors: Z
authors: Z
authors: Shen
authors: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors: F D
authors: FD
authors: Barr
authors: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
authors: A W
authors: AW
authors: Boesch
authors: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA.
authors: M E
authors: ME
authors: Ackerman
authors: Department of Medicine and UAB Center for AIDS Research, University of Alabama at Birmingham, Research Service Birmingham, Birmingham, Alabama, USA.|Birmingham Veterans Affairs Medical Center, Research Service Birmingham, Birmingham, Alabama, USA.
authors: J C
authors: JC
authors: Kappes
authors: Department of Medicine and UAB Center for AIDS Research, University of Alabama at Birmingham, Research Service Birmingham, Birmingham, Alabama, USA.
authors: C
authors: C
authors: Ochsenbauer
authors: Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors: C R
authors: CR
authors: Wira
mesh_terms: D039521:CD11c Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D053492:Elafin / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005836:Genitalia, Female / Q000276:immunology*; D006678:HIV / Q000276:immunology* / Q000472:pathogenicity; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D010587:Phagocytosis; D019713:Receptors, CCR5 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D039521:CD11c Antigen; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D053492:Elafin; D004958:Estradiol; D016209:Interleukin-8; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D019713:Receptors, CCR5; D011956:Receptors, Cell Surface; D053481:Secretory Leukocyte Peptidase Inhibitor; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C584933:CCR5 protein, human; C506814:SLPI protein, human