Probiotic lactobacillus and estrogen effects on vaginal epithelial gene expression responses to Candida albicans

Abstract

BackgroundVaginal epithelial cells have receptors, signal transduction mechanisms, and cytokine secretion capabilities to recruit host defenses against Candida albicans infections. This research evaluates how probiotic lactobacilli affect the defensive epithelial response.MethodsThis study used quantitative reverse transcription-polymerase chain reaction assay (qRT-PCR), flow cytometry, and a multiplex immunoassay to observe changes in the regulation of gene expression related to cytokine responses in the VK2 (E6/E7) vaginal epithelial cell line treated with 17β-estradiol, exposed to probiotic Lactobacillus rhamnosus GR-1® and Lactobacillus reuteri RC-14® and challenged with C. albicans. Data were statistically evaluated by repeated measures analysis of variance and paired t-tests where appropriate.ResultsC. albicans induced mRNA expression of genes related to inflammatory cytokine responses associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signal transduction pathways. 17β-estradiol suppressed expression of interleukin-1α (IL-1α), IL-6, IL-8, and tumor necrosis factor alpha (TNFα) mRNA. Probiotic lactobacilli suppressed C. albicans-induced nuclear factor-kappa B inhibitor kinase kinase alpha (Iκκα), Toll-like receptor-2 (TLR2), TLR6, IL-8, and TNFα, also suggesting inhibition of NF-κB signaling. The lactobacilli induced expression of IL-1α, and IL-1β mRNA, which was not inhibited by curcumin, suggesting that they induce an alternate inflammatory signal transduction pathway to NF-κB, such as the mitogen activated protein kinase and activator protein-1 (MAPK/AP-1) signal transduction pathway. Curcumin inhibited IL-13 secretion, suggesting that expression of this cytokine is mainly regulated by NF-κB signaling in VK2 cells.ConclusionsThe results suggest that C. albicans infection induces pro-inflammatory responses in vaginal epithelial cells, and estrogen and lactobacilli suppress expression of NF-κB-related inflammatory genes. Probiotic lactobacilli may induce IL-1α and IL-1β expression by an alternate signal transduction pathway, such as MAPK/AP-1. Activation of alternate signaling mechanisms by lactobacilli to modify epithelial cell cytokine production may be a mechanism for probiotic modulation of morbidity in vulvovaginal candidiasis.

Lactobacillus rhamnosus GR-1 Ameliorates Escherichia coli-Induced Inflammation and Cell Damage via Attenuation of ASC-Independent NLRP3 Inflammasome Activation

“…Pretreatment of pregnant CD-1 mice with L. rhamnosus GR-1 culture supernatant decreases lipopolysaccharide (LPS)-induced production of various cytokines and chemokines (4). Lactobacillus rhamnosus GR-1 suppresses expression of nuclear factor (NF)-B-related inflammatory genes and activates alternate mitogen-activated protein kinase (MAPK) and activator protein 1 pathways to recruit host defense factors in Candida albicans infection (5). Although several possible mechanisms underlying the beneficial effects of L. rhamnosus have been investigated, including direct antimicrobial action, as well as competitive exclusion of pathogens or inhibition of pathogen adhesion, enhancement of epithelial barrier function, and modulation of both local and systemic host immune responses (6), our previous studies demonstrated that pretreatment with high doses of L. rhamnosus may counteract the preventative effects (7,8).…”

The development of probiotics for women’s health

“…The latter effect might explain the increased cure of the disease when probiotic and antifungal therapies were conjointly administered (Martinez et al 2009b). Confirmatory studies have shown that L. rhamnosus can inhibit Candida biofilms through reduced hyphal differentiation (Matsubara et al 2016) and activation of IL-1␣ and IL-1␤ expression by an alternate signal transduction pathway (Wagner and Johnson 2012).…”

Lactobacillus rhamnosus pode alterar a virulência de Candida albicans

“…Observa-se uma associação entre a presença de lactobacilos na vagina e a redução do desenvolvimento de candidíase vulvovaginal. Uma avaliação de como os probióticos lactobacilos afetavam a resposta epitelial defensiva sugere que os lactobacilos suprimem a expressão de genes inflamatórios induzidos por Candida albicans, modulando a resposta imunológica do hospedeiro 5 .…”