Cervicovaginal levels of human beta defensins during bacterial vaginosis.

Nathalia Mayumi Noda-Nicolau,Giovana Fernanda Cosi Bento,Mariana De Castro Silva,Gabriel Vitor Silva Pinto,Márcia Guimarães Da Silva,Jeniffer Sena Baptista Ferreira,Júlia Andrade Pessoa Morales,Jossimara Polettini,Júlia Abbade Tronco,Juliano Novak,Aline Nascimento Bolpetti,Camila Marconi,Antonella Marangoni

doi:10.1371/journal.pone.0260753

Nathalia Mayumi Noda-Nicolau, Giovana Fernanda Cosi Bento + Show 11 more

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https://doi.org/10.1371/journal.pone.0260753

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Abstract

To compare the cervicovaginal levels of human beta defensin (hBD)-1, 2 and 3 of women according to the status of Nugent-defined bacterial vaginosis (BV). A total of 634 women of reproductive age were included in the study. Participants were equally distributed in two groups: according to the classification of vaginal smears according to Nugent criteria in normal (scores 0 to 3) and BV (scores ≥7). Cervicovaginal fluid samples were used for measurements of hBDs1, 2 and 3 levels by enzyme-linked immunosorbent assay (ELISA). Levels of each hBD were compared between the two study groups using Mann-Whitney test, with p-value <0.05 considered as significant. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for sociodemographic variables and hBD1-3 levels associated with BV a multivariable analysis. Correlation between Nugent score and measured levels of hBDs1-3 were calculated using Spearman's test. Cervicovaginal fluids from women with BV showed lower levels of hBD-1 [median 2,400.00 pg/mL (0-27,800.00); p<0.0001], hBD-2 [5,600.00 pg/mL (0-45,800.00); p<0.0001] and hBD-3 [1,600.00 pg/mL (0-81,700.00); p = 0.012] when compared to optimal microbiota [hBD-1: [median 3,400.00 pg/mL (0-35,600.00), hBD-2: 12,300.00 pg/mL (0-95,300.00) and hBD-3: 3,000.00 pg/mL (0-64,300.00), respectively]. Multivariable analysis showed that lower levels of hBD-1 (OR: 2.05; 95% CI: 1.46-2.87), hBD-2 (OR: 1.85; 95% CI: 1.32-2.60) and hBD-3 (OR: 1.90; 95% CI: 1.37-2.64) were independently associated BV. Significant negative correlations were observed between Nugent scores and cervicovaginal levels of hBD-1 (Spearman's rho = -0.2118; p = 0.0001) and hBD-2 (*Spearman's rho = -0.2117; p = 0.0001). Bacterial vaginosis is associated with lower cervicovaginal levels of hBDs1-3 in reproductive-aged women.

Highlights

Human beta defensins are antimicrobial peptides that have an important role in the innate immune response
Multivariable analysis showed that lower levels of human beta defensin (hBD)-1 (OR: 2.05; 95% confidence interval (95% CI): 1.46–2.87), hBD-2 (OR: 1.85; 95% CI: 1.32– 2.60) and hBD-3 (OR: 1.90; 95% CI: 1.37–2.64) were independently associated bacterial vaginosis (BV)
Significant negative correlations were observed between Nugent scores and cervicovaginal levels of hBD-1 (Spearman’s rho = -0.2118; p = 0.0001) and hBD-2 (*Spearman’s rho = -0.2117; p = 0.0001)

Summary

Introduction

Human beta defensins (hBDs) are antimicrobial peptides that have an important role in the innate immune response. They are small cationic peptides produced by epithelial and immunity cells. These peptides act by causing electrostatic imbalance leading to pores formation in the microbial membranes and cell lysis [1]. HBD-1 is recognized as the most important antimicrobial peptide of epithelial cells. HBD-2 is effective against Gram-negative and -positive bacteria [10]. HBD-3 is effective against Gram-negative and -positive bacteria [2, 8], and its production is induced by STAT-1 [12] and AP-1 [14, 15] transcription factors, while hBD-3 activation via NF-kappa B is still controversial [12, 14, 15]. In the context of the female genital tract, hBDs contribute for the protection of the vaginal environment against potential pathogens [16] and vaginal epithelial cells are important sources of hBDs [10, 17, 18]

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