Poster Presentation 9th Australasian Virology Society Meeting 2017

SHORT CHAIN FATTY ACIDS ASSOCIATED WITH BACTERIAL VAGINOSIS FAIL TO ELICIT ANTI-INFLAMMATORY EFFECTS ON ECTOCERVICAL EPITHELIAL CELLS (#152)

David Delgado Diaz 1 2 , David Tyssen 1 , Anna Hearps 1 3 , Raffi Gugasyan 1 4 , Gilda Tachedjian 1 3 5 6
  1. Burnet Institute, Melbourne, VIC, Australia
  2. Department of Microbiology, Monash University, Clayton, Australia
  3. Department of Infectious Diseases, Monash University, Melbourne, Australia
  4. Department of Immunology, Monash University, Melbourne, Australia
  5. Department of Microbiology and Immunology at Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia
  6. School of Sciences, College of Science, Engineering and Health, RMIT University, Melbourne, VIC, Australia

INTRODUCTION: Bacterial vaginosis (BV), characterised by an imbalance of the vaginal microbiome and genital inflammation, is a risk factor for transmitting and contracting human immunodeficiency virus (HIV). Lactic acid (LA), a vaginal microbiota metabolite (VMB) produced by lactobacilli, is elevated during vaginal eubiosis and elicits an anti-inflammatory effect on cervicovaginal epithelial cells that could protect against HIV. In contrast, BV is characterised by a dramatic depletion of LA and an increase in VMB's comprising short-chain fatty acids (SCFAs) and succinic acid (SA).  SCFAs elicit a proinflammatory response from PBMCs; however the impact of SCFAs on cervicovaginal epithelial cells is unknown. 

METHODS: Monolayers of ectocervical cells (Ect1/E6E7) were treated with combinations of VMB to mimic eubiotic and BV conditions in the absence or presence of TLR agonists (LPS, Poly I:C and Pam3CSK4) to simulate pathogen challenge. Cytokines and chemokines in the supernatant were quantified using a Luminex multiplex assay.

RESULTS: VMB representing BV conditions had no effect on the pro- and anti-inflammatory response of Ect1 cells. In the presence of TLR agonist stimulation, BV VMB had little effect on dampening cytokine/chemokine responses compared to eubiotic VMB. Increased production of the anti-inflammatory cytokine IL-1RA was observed after eubiotic VMB treatment both with and without TLR agonist stimulation, but not with VMB representing BV conditions. Increased secretion of pro-inflammatory cytokines IL-6 and IL-8 by TLR agonists was decreased under only eubiotic VMB conditions. Similarly, elevated IP-10, TNF, RANTES and MIP3α levels elicited by poly I:C treatment was only dampened by eubiotic VMB

CONCLUSION: In contrast to the anti-inflammatory effect of eubiotic VMB due to LA, VMB representing BV conditions failed to elicit immune modulatory effects on Ect1 cells and had little impact on dampening pro-inflammatory immune mediators elicited by TLR agonists consistent with the pro-inflammatory milieu associated with BV and increased HIV risk.