Abstract
Vaginal commensal lactobacilli are considered to contribute significantly to the control of vaginal microbiota by competing with other microflora for adherence to the vaginal epithelium and by producing antimicrobial compounds. However, the molecular mechanisms of symbiotic prokaryotic-eukaryotic communication in the vaginal ecosystem remain poorly understood. Here, we showed that both DNA methylation and histone modifications were associated with expression of the DEFB1 gene, which encodes the antimicrobial peptide human β-defensin-1, in vaginal keratinocyte VK2/E6E7 cells. We investigated whether exposure to Lactobacillus gasseri and Lactobacillus reuteri would trigger the epigenetic modulation of DEFB1 expression in VK2/E6E7 cells in a bacterial species-dependent manner. While enhanced expression of DEFB1 was observed when VK2/E6E7 cells were exposed to L. gasseri, treatment with L. reuteri resulted in reduced DEFB1 expression. Moreover, L. gasseri stimulated the recruitment of active histone marks and, in contrast, L. reuteri led to the decrease of active histone marks at the DEFB1 promoter. It was remarkable that distinct histone modifications within the same promoter region of DEFB1 were mediated by L. gasseri and L. reuteri. Therefore, our study suggested that one of the underlying mechanisms of DEFB1 expression in the vaginal ecosystem might be associated with the epigenetic crosstalk between individual Lactobacillus spp. and vaginal keratinocytes.
Highlights
Emerging evidence suggests a critical role for epigenetic mechanisms, such as DNA methylation and histone modifications, in modulating the expression of host genes during bacterial infections [1]
To determine whether epigenetic modulation of the DEFB1 gene occurs in human vaginal keratinocytes, we first examined the transcriptional restoration of DEFB1 in VK2/E6E7 cells after treatment with either the DNA methyltransferase inhibitor DAC or the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) (Fig. 1a)
Compared to the level in untreated cells, a remarkable elevation of the DEFB1 mRNA level was observed following DAC-induced DNA demethylation and TSA-mediated histone acetylation. These data imply that transcriptional regulation of DEFB1 in VK2/E6E7 cells is associated with epigenetic mechanisms involving both DNA methylation and histone deacetylation
Summary
Emerging evidence suggests a critical role for epigenetic mechanisms, such as DNA methylation and histone modifications, in modulating the expression of host genes during bacterial infections [1]. Commensal microbes can constitute the first line of defense against infection by participating in the maintenance of immune homeostasis through epigenetic modification of host genes. Probiotics, defined as live microorganisms that confer a health benefit on the host, have recently been found to induce antimicrobial peptides against pathogens in the gastrointestinal tract [3]. Vaginal lactobacilli produce antimicrobial compounds such as bacteriocins and hydrogen peroxide, and they are considered the most important probiotic strains among the normal flora of healthy individuals. Whether secretion of antimicrobial peptides such as defensins from vaginal epithelial cells is affected by exposure to Lactobacillus spp. in the female reproductive tract has not been determined so far
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
