Aberrant cervical innate immunity predicts onset of dysbiosis and sexually transmitted infections in women of reproductive age

Autoři: Raina N. Fichorova aff001;  Charles S. Morrison aff002;  Pai-Lien Chen aff003;  Hidemi S. Yamamoto aff001;  Yashini Govender aff001;  Damilola Junaid aff001;  Stanthia Ryan aff001;  Cynthia Kwok aff003;  Tsungai Chipato aff004;  Robert A. Salata aff005;  Gustavo F. Doncel aff006
Působiště autorů: Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States of America aff001;  Behavioral, Epidemiologic and Clinical Sciences, FHI, Durham, NC, United States of America aff002;  Biostatistics, FHI, Durham, NC, United States of America aff003;  University of Zimbabwe, Harare, Zimbabwe aff004;  Case Western Reserve University, Cleveland, OH, United States of America aff005;  CONRAD, Arlington, VA, United States of America aff006;  Eastern Virginia Medical School, Norfolk, VA, United States of America aff007
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224359


Sexually transmitted infections (STIs) and vaginal dysbiosis (disturbed resident microbiota presenting with abnormal Nugent score or candidiasis) have been associated with mucosal inflammation and risk of HIV-1 infection, cancer and poor reproductive outcomes. To date, the temporal relationships between aberrant cervical innate immunity and the clinical onset of microbial disturbance have not been studied in a large population of reproductive age women. We examined data from a longitudinal cohort of 934 Ugandan and Zimbabwean women contributing 3,274 HIV-negative visits who had complete laboratory, clinical and demographic data. Among those, 207 women later acquired HIV, and 584 women were intermittently diagnosed with C. trachomatis (CT), N. gonorrhoeae (NG), genital herpes (HSV-2), T. vaginalis (TV), candidiasis, and abnormal intermediate (4–6) or high (7–10) Nugent score, i.e. bacterial vaginosis (BV). Immune biomarker concentrations in cervical swabs were analyzed by generalized linear and mixed effect models adjusting for site, age, hormonal contraceptive use (HC), pregnancy, breastfeeding, genital practices, unprotected sex and overlapping infections. High likelihood ratios (1.5–4.9) denoted the values of cervical immune biomarkers to predict onset of abnormal Nugent score and candidiasis at the next visits. When controlling for covariates, higher levels of β-defensin-2 were antecedent to BV, CT and HSV-2, lower anti-inflammatory ratio IL-1RA:IL-1β–to intermediate Nugent scores and candida, lower levels of the serine protease inhibitor SLPI–to candida, lower levels of the adhesion molecule ICAM-1 –to TV, and lower levels of the oxidative stress mitigator and endothelial activation marker VEGF–to NG. Changes in innate immunity following onset of dysbiosis and infections were dependent on HC use when controlling for all other covariates. In conclusion, imminent female genital tract dysbiosis or infection can be predicted by distinct patterns of innate immunity. Future research should characterize biotic and abiotic determinants of this pre-existing innate immunity state.

Klíčová slova:

Biomarkers – Candida – HIV – Immune response – Immunity – Innate immune system – Microbiome – Sexually transmitted diseases


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