Relationship Between Human β-Defensin 2 and the Vaginal Environment

Abstract

As one of the main antimicrobial peptides, human β-defensin 2 (HBD2) plays multiple roles in the lower genital tract. Based on the Nugent score as a diagnostic criterion for bacterial vaginosis, we sought to clarify the correlations among the Nugent score and Interleukin-6 (IL-6) and HBD2 levels in vaginal secretions in association with various types of infection. Ninety-eight women were recruited for this study. Levels of HBD2 and IL-6 in the vaginal wash were measured by enzyme-linked immunosorbent assays. According to the Nugent method, the number of Lactobacillus morphotypes per field of view was well correlated with the HBD2 level. The amount of HBD2 was also well correlated with the presence of Candida spp.(p<0.01). In vitro experiments revealed that the expression of HBD2 from the human vaginal epithelial cell line, VK2/E6E7, was induced by the addition of heat-killed Candida albicans (HKCA). The addition of HKCA induced the expression of Dectin-1 mRNA, and a luciferase assay for NF-kB responsive elements showed that HKCA activated NF-kB signaling. These results suggested that Candida albicans would be induced the activation of Dectin-1 and NF-kB signaling, resulting in HBD2 expression. In conclusion, the expression of HBD2 was positively correlated with the presence of Lactobacillus and Candida spp..

Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response

“…Women in early pregnancy who suffer from bacterial vaginosis have significantly lower hBD-2 concentrations in vaginal samples compared to healthy women [ 113 ]. In contrast, increased secretion of hBD-2 by the human vaginal epithelial cell line (VK2/E6E7) after stimulation with Candida albicans was described in in vitro studies [ 121 ]. In studies of the amniotic fluid, hBD-2 was present in all samples, but its concentration increased significantly during intra-amniotic infections [ 114 ].…”

Cervicovaginal levels of human beta defensins during bacterial vaginosis

“…The association between hBDs and BV in reproductive-aged women has been poorly studied to date, and most of them are based on a very limited sample size [ 18 , 28 ]. Our study included a total of 634 measured samples and showed that BV has lower levels of hBD-1, -2 and -3.…”

“…crispatus in cervicovaginal lavage samples from healthy women. Accordingly, Kotani et al [ 18 ] reported the Nugent score for Lactobacillus morphotype point was well correlated with hBD-2. Additionally, studies using intestinal epithelial cell cultures demonstrate that Lactobacillus spp.…”

“…hBD-3 is also 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 ].…”

Antimicrobial Peptides with Anti-Candida Activity

“…C. albicans responds to HBD-2 and HBD-3, executing a response to osmotic stress by activating the high-osmolarity glycerol (HOG) pathway [ 41 ]. The quantity of HBD-2 in the presence of C. albicans is augmented in the lower genital tract of women [ 42 ]. In addition, the presence of HBD-2 and HBD-3 is correlated with a better protection of the gut during C. albicans infections, as they promote the creation of tight junctions between the epithelial cells of the intestinal mucosa [ 43 ].…”