Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition

Hearps, A, Tyssen, D, Srbinovski, D, Bayigga, L, Diaz, D, Aldunate, M, Cone, R, Gugasyan, R, Anderson, D and Tachedjian, G 2017, 'Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition', Mucosal Immunology, vol. 10, no. 6, pp. 1480-1490.


Document type: Journal Article
Collection: Journal Articles

Title Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition
Author(s) Hearps, A
Tyssen, D
Srbinovski, D
Bayigga, L
Diaz, D
Aldunate, M
Cone, R
Gugasyan, R
Anderson, D
Tachedjian, G
Year 2017
Journal name Mucosal Immunology
Volume number 10
Issue number 6
Start page 1480
End page 1490
Total pages 11
Publisher Nature
Abstract Inflammation in the female reproductive tract (FRT) is associated with increased HIV transmission. Lactobacillus spp. dominate the vaginal microbiota of many women and their presence is associated with reduced HIV acquisition. Here we demonstrate that lactic acid (LA), a major organic acid metabolite produced by lactobacilli, mediates anti-inflammatory effects on human cervicovaginal epithelial cells. Treatment of human vaginal and cervical epithelial cell lines with LA (pH 3.9) elicited significant increases in the production of the anti-inflammatory cytokine IL-1RA. When added simultaneously or prior to stimulation, LA inhibited the Toll-like receptor agonist-elicited production of inflammatory mediators IL-6, IL-8, TNFα, RANTES, and MIP3α from epithelial cell lines and prevented IL-6 and IL-8 production by seminal plasma. The anti-inflammatory effect of LA was mediated by the protonated form present at pH≤3.86 and was observed with both L- and D-isomers. A similar anti-inflammatory effect of LA was observed in primary cervicovaginal cells and in an organotypic epithelial tissue model. These findings identify a novel property of LA that acts directly on epithelial cells to inhibit FRT inflammation and highlights the potential use of LA-containing agents in the lower FRT as adjuncts to female-initiated strategies to reduce HIV acquisition.
Subject Biological Sciences not elsewhere classified
Keyword(s) Female Reproductive-Tract
Innate Immune Activation
Genital-Tract
Bacterial Vaginosis
Gene-Expression
Humanmonocytes
Seminal Plasma
Target-Cells
Kappa-B
Women
DOI - identifier 10.1038/mi.2017.27
Copyright notice © 2017 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License.
ISSN 1933-0219
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