P06.10 Lactic acid dampens inflammatory responses elicited by microbial tlr agonists from vaginal and cervical epithelial cells

Abstract

Introduction Vaginal lactobacilli are associated with favourable sexual health outcomes and acidify the vagina to pH Methods The effect of apically applied L-LA (0.3% w/w, pH3.9) was assessed on vaginal (VK2), endocervical (End), ectocervical (Ect) epithelial cell lines and primary ectocervical cells grown in transwells. Elicited immune mediators were quantified following apical stimulation with toll-like receptor (TLR) agonists ± L-LA by flow cytometry and luminex-based assays. Results L-LA had little impact on FRT epithelial cell viability. Stimulation of FRT epithelial cell lines with the TLR3-agonist poly (I:C) (PIC) induced high-levels of pro-inflammatory cytokines (IL-6/IL-8), and their variable induction with TLR agonists Pam (3) CSK(4) (TLR1/2) and lipopolysaccharide (TLR4). Conversely, L-LA treatment significantly reduced PIC-induced IL-6 (~30-fold) and IL-8 (3–4.5–fold, p£0.03) secretion, compared to PIC-only treated FRT epithelial cell lines. Irrespective of TLR stimulation, L-LA elicited a 4–11-fold (p Conclusion L-LA found in lactobacillus -dominated vaginal microbiota elicits an anti-inflammatory effect on lower FRT epithelial cells and dampens inflammation induced by microbial TLR agonists suggesting a role in mitigating inflammation-induced HIV susceptibility at the vaginal mucosa. Disclosure of interest statement This study was funded by NHMRC Project APP1088564. No pharmaceutical grants were received in the development of this study.