Immunoregulatory Effects Triggered by Lactic Acid Bacteria Exopolysaccharides: New Insights into Molecular Interactions with Host Cells

Abstract

Researchers have demonstrated that lactic acid bacteria (LAB) with immunomodulatory capabilities (immunobiotics) exert their beneficial effects through several molecules, including cell wall, peptidoglycan, and exopolysaccharides (EPS), that are able to interact with specific host cell receptors. EPS from LAB show a wide heterogeneity in its composition, meaning that biological properties depend on the strain and. therefore, only a part of the mechanism of action has been elucidated for these molecules. In this review, we summarize the current knowledge of the health-promoting actions of EPS from LAB with special focus on their immunoregulatory actions. In addition, we describe our studies using porcine intestinal epithelial cells (PIE cells) as a model to evaluate the molecular interactions of EPS from two immunobiotic LAB strains and the host cells. Our studies showed that EPS from immunobiotic LAB have anti-inflammatory capacities in PIE cells since they are able to reduce the production of inflammatory cytokines in cells challenged with the Toll-like receptor (TLR)-4-agonist lipopolysaccharide. The effects of EPS were dependent on TLR2, TLR4, and negative regulators of TLR signaling. We also reported that the radioprotective 105 (RP105)/MD1 complex, a member of the TLR family, is partially involved in the immunoregulatory effects of the EPS from LAB. Our work described, for the first time, that LAB and their EPS reduce inflammation in intestinal epithelial cells in a RP105/MD1-dependent manner. A continuing challenge for the future is to reveal more effector-receptor relationships in immunobiotic-host interactions that contribute to the beneficial effects of these bacteria on mucosal immune homeostasis. A detailed molecular understanding should lead to a more rational use of immunobiotics in general, and their EPS in particular, as efficient prevention and therapies for specific immune-related disorders in humans and animals.

Comprehensive mapping of the cell response to E. coli infection in porcine intestinal epithelial cells pretreated with exopolysaccharide derived from Lactobacillus reuteri

“…TLR signalling pathways play crucial roles in the regulation and activation of numerous pro-inflammatory molecules. LPS is a well-known activator of TLR4 [36]; however, recent studies have shown that EPS from lactic acid bacteria can also activate TLR4, TLR2 [5] and C-type lectin signalling pathways [7]. Activation of TLR4 induced downstream MyD88-dependent and TRIFdependent (MyD88-independent) pathways, which in turn led to a cascade of activated molecules, such as NF-κB, activator protein-1 (AP-1), interferon regulatory factor 5 (IRF5) and IRF3 (type I interferons) and, finally, inflammatory cytokines [49] (Additional file 6).…”

“…In the cells pretreated with EPS and then infected with E. coli, the highest fold change was observed for the gene encoding CD14 (logFC of 7.87), while the gene encoding CD180 was the downregulated to the greatest extent (logFC of −4.26). The CD14 molecule is a coreceptor for bacterial LPS [32], and CD180 (also known as RP105) is a negative regulator of TLR4 [5]. The expression of these genes was also altered in the E. coli-infected cells (CD14, logFC of 5.95; CD180, logFC of −3.73) but not in the cells treated only with EPS.…”

“…Among the beneficial bacteria, Lactobacillus represents one of the best producers of EPS. Exopolysaccharides produced by lactobacilli have not only positive effects on their producers [2,3] but also immunomodulatory effects on the gut mucosal immune system [4][5][6]. Exopolysaccharides stimulate the immune response in intestinal epithelial cells (IECs) through the activation of C-type lectin receptors (CLRs).…”

Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases

“…Many of these studies (12–26) employ bacteria that have been termed “immunobiotics,” which have been defined as probiotic strains that are able to beneficially regulate mucosal immunity (27, 28). Immunobiotics are recognized by the pattern recognition receptors of epithelial and antigen-presenting cells such as dendritic cells and macrophages, and these immunobiotics are known to beneficially regulate innate and adoptive immune responses (Figure 1C); there have been tremendous advances in the clarification of strain-specific immune regulation functions at the cellular and molecular levels (28–32). …”

Probiotic Microorganisms: A Closer Look

“…In the review of Laiño et al, [11], the current knowledge of the health-promoting actions of EPS from probiotic bacteria with special focus on their immunoregulatory actions are summarized. In addition, the article describes the studies evaluating the molecular interactions of EPS from probiotics with intestinal epithelial cells, and highlights the role of the pattern recognition receptors and their signaling pathways in the anti-inflammatory capacities of probiotic EPS.…”