Lactic acid stimulates interleukin-23 production by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide

Abstract

Lactic acid is the predominant acid present in the vagina. We evaluated the consequences of lactic acid, at physiological levels present in the vagina, on cytokine responses of peripheral blood mononuclear cells (PBMCs) obtained from 10 individuals in the presence or absence of bacterial lipopolysaccharide. Preincubation of PBMCs in 15 mM lactic acid before the addition of lipopolysaccharide resulted in a 246% mean increase in interleukin-23 (IL-23) secretion over that released in the presence of lipopolysaccharide alone (P = 0.0068). The lipopolysaccharide-induced production of tumor necrosis factor-a, IL-6, IL-10 and IL-12 was unaffected by lactic acid. IL-23 stimulation was not observed if the lactic acid was neutralized before its addition to the culture medium or if hydrochloric acid was substituted for lactic acid. In the absence of lipopolysaccharide, lactic acid did not stimulate the production of IL-23 or any of the other cytokines. The increase in IL-23 production was proportional to the lactic acid concentration over a 15-60 mM range. We conclude that at body sites characterized by lactic acid accumulation, such as in the human vagina, exposure to gram-negative bacteria results in selective IL-23 production, leading to a subsequent preferential stimulation of the Th17 T lymphocyte pathway.

The vaginal microbiome, vaginal anti‐microbial defence mechanisms and the clinical challenge of reducing infection‐related preterm birth

“…In the presence of a synthetic analogue of double-stranded viral RNA, lactic acid potentiates the production of protective pro-inflammatory cytokines by vaginal epithelial cells. 29 Lactic acid also promotes activation of the T helper type 17 subclass of helper T lymphocytes, 30 stimulates dendritic cell maturation 31 and induces interferon-c production. 32 Each of these activities enhances activation of anti-microbial innate or acquired immunity.…”

Use of lactobacilli and estriol combination in the treatment of disturbed vaginal ecosystem: a review

“…The acidic environment provides optimal conditions for the lactobacilli and unfavourable growth conditions for the pathogenic micro-organisms (1,16). Lactic acid has been also shown to stimulate the immune response (17). In vitro experiments with L. acidophilus KS400 have demonstrated that the strain is able to produce substantial amounts of lactic acid (16).…”

The Microbiome at Other Mucosal Sites

“…The vaginal stratified epithelium produces glycogen and other carbohydrates that are used by Lactobacillus species to produce lactic acid ; in return, the acidic environment protects the vaginal mucosa from colonization with pathogens such as Neisseria, other Gramnegative bacteria, and even HIV virus (Graver and Wade, 2011;Lai et al, 2009;Witkin et al, 2011). Lactobacilli may also protect against pathogenic bacteria through the production of bacteriocins such hydrogen peroxide (Fichorova et al, 2011;Hawes et al, 1996;Hillier et al, 1993).…”