Anti-inflammatory effect of two Lactobacillus strains during infection with Gardnerella vaginalis and Candida albicans in a HeLa cell culture model

Abstract

Lactobacilli are the dominant bacteria of the vaginal tract of healthy women and they play a major role in the maintenance of mucosal homeostasis, preventing genital infections, such as bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). It is now known that one mechanism of this protection is the influence that lactobacilli can exert on host immune responses. In this context, we evaluated two Lactobacillus strains (L. plantarum 59 and L. fermentum 137) for their immunomodulatory properties in response to Gardnerella vaginalis (BV) or Candida albicans (VVC) infections in a HeLa cell infection model. G. vaginalis and C. albicans triggered the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) and the activation of NF-κB in HeLa cells, in contrast to L. plantarum 59 and L. fermentum 137. Treatments with the Lactobacillus strains or their cell-free supernatants before (pre-treatment) or after (post-treatment) the challenge with the pathogens resulted in decreased secretion of pro-inflammatory cytokines and decreased activation of NF-κB. The treatments with Lactobacillus strains not only decreased the secretion of IL-8, but also its expression, as confirmed by gene reporter luciferase assay, suggesting transcription-level control by lactobacilli. In conclusion, L. plantarum 59 and L. fermentum 137 were confirmed to have an anti-inflammatory effect against G. vaginalis and C. albicans and they were able to influence signalling in NF-κB pathway, making them interesting candidates as probiotics for the prevention or treatment of BV and VVC.

Inflammatory and antimicrobial properties differ between vaginal Lactobacillus isolates from South African women with non-optimal versus optimal microbiota

“…In this study, incubation of vaginal epithelial cells with G. vaginalis alone caused significant upregulation of multiple inflammatory cytokines (IL-6, IL-8, IL-1α, MIP-1α, MIP-1β and MIP-3α), while pre-incubation with lactobacilli resulted in significant downregulation of IL-6 and IL-8 and nonsignificant downregulation of each of the chemokines evaluated. These findings are similar to previous studies showing that G. vaginalis induces inflammatory responses both in vitro and in vivo and lactobacilli have immunoregulatory properties in vitro and are associated with low inflammatory cytokine levels in vivo 28,32,33 . Although the majority of inflammatory cytokines and chemokines were lower following pre-incubation with lactobacilli prior to incubation with G. vaginalis, we found that IL-1α and IL-1β production was significantly higher compared to G. vaginalis and Lactobacillus only cultures.…”

Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway

“…disorders [31][32][33][34] . L. rhamnosus (4B15) and L. gasseri (4M13) have been reported to have antioxidative activity, inhibit α-glucosidase activity, reduce cholesterol, and suppress NO production.…”

Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota

“…Genital inflammation, driven by a highly diverse vaginal microbiota, and increased cervicovaginal levels of proinflammatory cytokines and chemokines are associated with higher levels of HIV transmission (Masson et al, 2015;Gosmann et al, 2017). Beneficial vaginal lactobacilli (e.g., L. crispatus) dampen inflammatory and inhibit pro-inflammatory responses mediated by TLR agonists (Rose et al, 2012;Doerflinger et al, 2014) and vaginal pathogens (Santos et al, 2018), and we have demonstrated that this effect is mediated, at least in part, by LA (Hearps et al, 2017). Here, we asked whether this effect is maintained in the presence of physiological concentrations of other vaginal organic acid metabolites.…”