Introduction Inflammation in the female reproductive tract (FRT) promotes while Lactobacillus spp. protect women from HIV acquisition. We assessed if lactic acid (LA), a major acid metabolite produced by lactobacilli, decreases inflammatory mediators produced by cervicovaginal epithelium.
Methods LA at physiological levels and pH were added apically to human vaginal or cervical epithelial cells and an organotypic tissue model cultured in transwells. Cells were stimulated apically with bacterial or viral mimicking TLR agonists, TNF or genital fluids (data collected in 2017). Cytokines and chemokines were quantified by luminex-based assays.
Results LA (pH 3.9) treatment of epithelial cell lines elicited significant increases in the anti-inflammatory cytokine IL-1RA. When added simultaneously to stimulation, LA inhibited the TLR agonist-induced production of inflammatory mediators IL-6, IL-8, TNFα, RANTES and MIP3α. The same LA anti-inflammatory effects were not recapitulated with media acidified to the same pH with HCl, and was mediated by the protonated form of LA present at pH ≤3.9. Both l- and d-isomers of LA elicited similar anti-inflammatory effects. LA pretreatment of cells for 1 hour, followed by cell washing and TLR agonist stimulation, inhibited pro-inflammatory production indicating a direct effect on cells. A similar anti-inflammatory effect of LA was observed in primary cervicovaginal cells and in an organotypic epithelial tissue model, and when FRT epithelial cells were exposed to either cervicovaginal or seminal fluids. Immune mediators were elicited by LA at physiological levels and pH that had little impact on cell viability or monolayer/tissue integrity.
Conclusion LA acts on FRT epithelial cells to inhibit inflammation that might explain in part the HIV protective properties of LA producing lactobacilli. This study highlights the potential use of LA-containing agents or LA-producing probiotics as adjuncts to female-initiated HIV prevention strategies
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