title: Cross-Sectional Analysis of Selected Genital Tract Immunological Markers and Molecular Vaginal Microbiota in Sub-Saharan African Women, with Relevance to HIV Risk and Prevention.
abstract: Data on immune mediators in the genital tract and the factors that modulate them in sub-Saharan women are limited. Cervicovaginal lavage (CVL) samples from 430 sexually active women from Kenya, South Africa, and Rwanda were analyzed for 12 soluble immune mediators using Bio-Plex and Meso Scale Discovery multiplex platforms, as well as single enzyme-linked immunosorbent assays. Ten bacterial species were quantified in vaginal swab samples. Bacterial vaginosis (BV) was defined by Nugent scoring. CVL samples from HIV-infected women showed a clear-cut proinflammatory profile. Pregnant women, adolescents, and women engaging in traditional vaginal practices differed in specific soluble markers compared to reference groups of adult HIV-negative women. Cervical mucus, cervical ectopy, abnormal vaginal discharge, and having multiple sex partners were each associated with an increase in inflammatory mediators. The levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12(p70), and IL-8 were elevated, whereas the IL-1RA/IL-1(α+β) ratio decreased in women with BV. The level of gamma interferon-induced protein 10 was lower in BV-positive than in BV-negative women, suggesting its suppression as a potential immune evasion mechanism by BV-associated bacteria. Lactobacillus crispatus and Lactobacillus vaginalis were associated with decreased proinflammatory cytokines and each BV-associated species with increased proinflammatory cytokines. Remarkably, the in vitro anti-HIV activity of CVL samples from BV-positive women was stronger than that of BV-negative women. In conclusion, we found significant associations of factors, including vaginal microbiota, which can influence immune mediators in the vaginal environment in sexually active women. These factors need to be considered when establishing normative levels or pathogenic cutoffs of biomarkers of inflammation and associated risks in African women.
authors.affiliation: Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Kyongo
authors.affiliation: HIV/STI Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Tania
authors.initials: T
authors.lastname: Crucitti
authors.affiliation: Clinical Trials Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Joris
authors.initials: J
authors.lastname: Menten
authors.affiliation: HIV/STI Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium Unit of Epidemiology and Control of HIV/STD, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Hardy
authors.affiliation: Faculty of Medicine and Health Sciences, Department of Microbiology, Immunology, and Clinical Chemistry, Ghent University, Ghent, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Cools
authors.affiliation: Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Michiels
authors.affiliation: Wits Reproductive Health and HIV Institute, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Sinead
authors.initials: S
authors.lastname: Delany-Moretlwe
authors.affiliation: International Center for Reproductive Health, Mombasa, Kenya.
authors.forename: Mary
authors.initials: M
authors.lastname: Mwaura
authors.affiliation: Rinda Ubuzima, Kigali, Rwanda.
authors.forename: Gilles
authors.initials: G
authors.lastname: Ndayisaba
authors.affiliation: MRC Clinical Trials Unit at University College London, London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Joseph
authors.affiliation: Laboratory of Genital Tract Biology, Department of Obstetrics, Gynaecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Raina
authors.initials: R
authors.lastname: Fichorova
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Janneke
authors.initials: J
authors.lastname: van de Wijgert
authors.affiliation: Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium Faculty of Pharmaceutical, Veterinary, and Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.affiliation: Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Ariën
authors.affiliation: Unit of Epidemiology and Control of HIV/STD, Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium vjespers@itg.be.
authors.forename: Vicky
authors.initials: V
authors.lastname: Jespers
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D054357:Chemokine CXCL10 / Q000276:immunology; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis* / Q000276:immunology*; D007378:Interleukins / Q000032:analysis / Q000276:immunology; D007630:Kenya; D007778:Lactobacillus / Q000235:genetics / Q000276:immunology; D064307:Microbiota; D011247:Pregnancy; D012432:Rwanda; D013019:South Africa; D014621:Vagina / Q000276:immunology* / Q000382:microbiology*; D044364:Vaginal Douching; D016585:Vaginosis, Bacterial / Q000276:immunology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; D018836:Inflammation Mediators; D007378:Interleukins