Immunomodulatory activity of Lactobacillus fermentum UCO-979C in gastric epithelial cells and its effect against Helicobacter pylori infection

GABRIELA MARRANZINO; JULIO VILLENA; VALERIA GARCIA; SUSANA ALVAREZ; SUSANA SALVA; APOLINARIA GARCIA

San Miguel de Tucumán

Simposio; V Simposio Internacional de Bacterias Lácticas (SIBAL); 2016

CERELA-CONICET

Helicobacter pylori colonizes the gastric mucosa of more than half of the world population. An aggressive pro-inflammatory immune response is generated in the gastric tissue resulting in gastritis and a series of morphological changes that increase the susceptibility to cancer development. The use of immunomodulatory lactic acid bacteria (immunobiotics) has been proposed to reduce the severity of chronic inflammatory-mediated tissue damage and to improve protective immunity against H. pylori. We previously isolated Lactobacillus fermentum UCO-979C from human gastric tissue and demonstrated that this bacterium is able to reduce the adherence of H. pylori to human gastric epithelial cells (AGS cells). In this work, we evaluated the capacity of L. fermentum UCO-979C to beneficially modulate immune response of AGS cells in response to H. pylori infection. For this purpose, AGS cells were treated with different doses of L. fermentum UCO-979C (105,106 or 107 cells/ml) and then challenged with H. pylori 43504 (107 cells/ml). Pathogen counts, cell viability, cellular damage and levels of TNF-α, IL-1β, IL-6, TGF-β, CCL20 and IL-8 were determined 24 hours after the challenge. It was observed that UCO-979C is able to protect AGS cells against H. pylori infection in a dose dependent manner. Results also showed a lesser H. pylori colonization of AGS cells when they were treated with the smaller dose of UCO-979C strain (Adhesion-%: UCO979C=45.6, control=100). This finding correlated with a higher viability (MTT-%: UCO979C=95, control=73) and a decreased cytotoxicity (LDH-UI/L: UCO979C=56.4±3.7, control=125.7±4.6) of AGS cells infected with H. pylori when compared to the infected control. When pro- and anti-inflammatory cytokines were evaluated, a significant decrease in the production of pro-inflammatory cytokines and chemokines and an increase in the immunoregulatory cytokine TGF-β was observed in UCO-979C-treated cells when compared to the infected control. Once again, the most notorious effects were achieved by the smaller dose of L. fermentum UCO-979C (TNF-α-pg/mL: UCO979C=73.2±3.6, control=195.8±3.6; TGF-β-pg/mL: UCO979C=195.7±5.9, control=255.9±5.5). These findings strongly support the possible immunobiotic potential of L. fermentum UCO-979C and provide evidence of its beneficial effects against the inflammatory damage induced by H. pylori infection. Considering the complexities of in vivo cellular interactions, it is necessary to complement these studies by evaluating the effect of L. fermentum UCO-979C on immunocompetent cells and its immunomodulatory effect in a H. pylori infection animal model.