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.
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.
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia.
authors.forename: A C
authors.initials: AC
authors.lastname: Hearps
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Tyssen
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Srbinovski
authors.affiliation: Departments of Obstetrics and Gynecology, Microbiology and Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bayigga
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: D J D
authors.initials: DJD
authors.lastname: Diaz
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|Department of Microbiology, Monash University, Clayton, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Aldunate
authors.affiliation: Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Cone
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|Department of Immunology, Monash University, Melbourne, Victoria, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Gugasyan
authors.affiliation: Departments of Obstetrics and Gynecology, Microbiology and Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Anderson
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.|Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia.|Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.|School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Tachedjian
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology* / Q000821:virology; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D007778:Lactobacillus; D064307:Microbiota; D014621:Vagina / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D019344:Lactic Acid