elafin and Vaginosis--Bacterial

Bacterial vaginosis is a common reproductive infection in which commensal vaginal lactobacilli are displaced by a mixed population of pathogenic bacteria. Bacterial vaginosis increases susceptibility to HIV, and it has been suggested that host innate immune responses to pathogenic bacteria contribute to enhanced infection, yet the cellular mechanisms mediating the increased HIV susceptibility remain uncharacterized. We evaluated the HIV-enhancing effects of bacterial vaginosis by inoculating endocervical epithelia with Atopobium vaginae, a bacterial vaginosis-associated bacteria, and assaying secreted factors for HIV-enhancing activity. When epithelia and A. vaginae were cocultured, we observed increased HIV-enhancing activity mediated by secreted low molecular weight factors. From this complex mixture we identified several upregulated host proteins, which functioned in combination to enhance HIV infection. These studies suggest that the host immune response to bacterial vaginosis-associated bacteria results in the release of HIV-enhancing factors. The combined activity of bacterial vaginosis-induced proteins likely mediates HIV enhancement.

Topics: Actinobacteria; Acute-Phase Proteins; Cell Line; Cervix Uteri; Cyclophilin A; Disease Susceptibility; Elafin; Female; HIV Infections; HIV-1; Host-Pathogen Interactions; Humans; Immunity, Innate; Lipocalin-2; Lipocalins; Mucous Membrane; Proteins; Proto-Oncogene Proteins; Up-Regulation; Vaginosis, Bacterial; WAP Four-Disulfide Core Domain Protein 2

To examine cervicovaginal elafin production in pregnancy and determine its relationship in bacterial vaginosis.. Samples of cervicovaginal secretions were collected from women with uncomplicated singleton pregnancies (n = 112) below 20 weeks gestation. Bacterial flora was assessed using Nugent's criteria, and levels of elafin were measured by enzyme-linked immunosorbent serologic assay (ELISA). Elafin expression in the cervix was also examined by immunohistochemistry. In vitro expression of elafin was examined using cervix and vaginal cell lines.. Elafin is expressed in the cervical glandular epithelium. Elafin was found in all 112 samples of cervicovaginal secretions and levels were diminished in women with bacterial vaginosis (P < .05). Interleukin 1beta (IL-1beta) stimulated elafin expression in cells derived from the endocervix, but not in those derived from the vaginal epithelium.. Elafin is a component of cervicovaginal secretions in pregnancy, and levels are diminished in bacterial vaginosis. It may be an important component of innate immunity in the lower genital tract.

Topics: Adult; Cell Line; Cervix Uteri; Down-Regulation; Elafin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Interleukin-1beta; Interleukin-8; Mucous Membrane; Pregnancy; Pregnancy Trimester, First; RNA, Messenger; Vagina; Vaginosis, Bacterial