Description
Immunoregulatory properties of clinical Lactobacillus isolates from South African women at high risk of HIV acquisition
Monalisa T. Manhanzva1, Andrea Abrahams1, Hoyam Gamieldien1, Heather Jaspan1,2, Shameem Jaumdally1, Shaun L. Barnabas1, Smritee Dabee1, Lindi Masson1,3*
1Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa; 2Seattle Children's Research Institute, University of Washington, Seattle, Washington, USA; 3Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa
Background: Female genital tract (FGT) inflammation increases HIV infection susceptibility. Bacterial vaginosis (BV), characterised by depletion of Lactobacillus species and an overgrowth of BV-associated bacteria, is associated with genital tract inflammation. Lactobacillus species may protect against HIV partly by reducing inflammation in the FGT. We aimed to evaluate immunoregulatory properties of vaginal Lactobacillus isolates from South African women.
Methods: Eighty lactobacilli isolated from cervicovaginal fluid collected from BV positive and negative women were identified to species level by MALDI-TOF biotyping. We measured production of cytokines (IL-6, IL-8, IL-1α, IL-1β, IP-10, MIP-3α, MIP-1α, MIP-1β, IL-1RA) by vaginal epithelial cells in response to each Lactobacillus isolate, as well as Gardnerella vaginalis, in the presence or absence of lactobacilli using Luminex. We evaluated Lactobacillus growth rates, adhesion, culture pH, D-lactate and L-lactate production.
Results: Lactobacilli from BV positive women were more inflammatory than those from BV negative women with respect to IL-6, IL-8, IL-1, IL-1, MIP-1 and MIP-1 production. All lactobacilli suppressed IL-6 [adjusted (adj.) p=0.0003] and IL-8 (adj. p=0.0170) responses to G. vaginalis. Overall, lactobacilli from BV negative women suppressed inflammatory cytokine responses to G. vaginalis to a greater degree than isolates from BV positive women. Lactobacilli adhesion correlated negatively with IL-6, IL-8, MIP-1, IL-1 and IL-1RA, while IL-6 concentrations were inversely associated with D-lactate production.
Conclusion: Vaginal lactobacilli suppress inflammatory responses to G. vaginalis, and may decrease HIV acquisition risk by reducing inflammation in the FGT. Lactobacilli from BV positive women were more inflammatory compared with lactobacilli from BV negative women.