Genomic Characterization of Lactobacillus delbrueckii TUA4408L and Evaluation of the Antiviral Activities of its Extracellular Polysaccharides in Porcine Intestinal Epithelial Cells

Abstract

In lactic acid bacteria, the synthesis of exopolysaccharides (EPS) has been associated with some favorable technological properties as well as health-promoting benefits. Research works have shown the potential of EPS produced by lactobacilli to differentially modulate immune responses. However, most studies were performed in immune cells and few works have concentrated in the immunomodulatory activities of EPS in non-immune cells such as intestinal epithelial cells. In addition, the cellular and molecular mechanisms involved in the immunoregulatory effects of EPS have not been studied in detail. In this work, we have performed a genomic characterization of Lactobacillus delbrueckii subsp. delbrueckii TUA4408L and evaluated the immunomodulatory and antiviral properties of its acidic (APS) and neutral (NPS) EPS in porcine intestinal epithelial (PIE) cells. Whole genome sequencing allowed the analysis of the general features of L. delbrueckii TUA4408L genome as well as the characterization of its EPS genes. A typical EPS gene cluster was found in the TUA4408L genome consisting in five highly conserved genes epsA-E, and a variable region, which includes the genes for the polymerase wzy, the flippase wzx, and seven glycosyltransferases. In addition, we demonstrated here for the first time that L. delbrueckii TUA4408L and its EPS are able to improve the resistance of PIE cells against rotavirus infection by reducing viral replication and regulating inflammatory response. Moreover, studies in PIE cells demonstrated that the TUA4408L strain and its EPS differentially modulate the antiviral innate immune response triggered by the activation of Toll-like receptor 3 (TLR3). L. delbrueckii TUA4408L and its EPS are capable of increasing the activation of interferon regulatory factor (IRF)-3 and nuclear factor κB (NF-κB) signaling pathways leading to an improved expression of the antiviral factors interferon (IFN)-β, Myxovirus resistance gene A (MxA) and RNaseL.

Immunobiotic Strains Modulate Toll-Like Receptor 3 Agonist Induced Innate Antiviral Immune Response in Human Intestinal Epithelial Cells by Modulating IFN Regulatory Factor 3 and NF-κB Signaling

“…In this regard, we have evaluated whether LAB strains induce the expression of IFN-β in HCT116 cells. We found that LABs stimulation increased the expression of IFN-β in response to PolyI:C. Our findings are in good agreement with the results of others studies obtained for Bifidobacterium infantis MCC12 and B. breve MCC1274 (3), Lactobacillus casei MEP221106 (16), Lactobacillus delbrueckii TUA4408L (29), and L. casei Zhang (34). Probiotic L. acidophilus NCFM was able to increase the expression of IFN-β in bone marrow derived dendritic cells in vitro (35).…”

Lipoteichoic Acid Is Involved in the Ability of the Immunobiotic Strain Lactobacillus plantarum CRL1506 to Modulate the Intestinal Antiviral Innate Immunity Triggered by TLR3 Activation

“…Research from the last decade investigating the immunobiotic effector molecules has demonstrated that each individual immunobiotic strain has a characteristic set of molecules, which are responsible of its interaction with the host's immune receptors (28)(29)(30). Surface molecules of immunobiotic microorganisms, including exopolysaccharides, cell wall peptidoglycan, and LTA, have been frequently associated with their immunomodulatory effects (28,29,31,32). In this regard, several reports have emphasized the importance of LTA in the immunomodulatory properties of some probiotic lactobacilli.…”

Exopolysaccharides From Streptococcus thermophilus ST538 Modulate the Antiviral Innate Immune Response in Porcine Intestinal Epitheliocytes

“…However, the ability of EPSs derived from LAB to differentially modulate the innate antiviral immune response in IECs was not addressed in details before. In this regard, we have previously investigated the capacity of EPSs produced by the immunobiotic strains Lactobacillus delbrueckii OLL1073R-1 (Kanmani et al, 2018a) and Lactobacillus delbrueckii TUA4408L (Kanmani et al, 2018b) to beneficially modulate the innate immune response in PIE cells. This in vitro system has been particularly useful for the FIGURE 5 | Effect of cell-free supernatants (CS) from Streptococcus thermophilus ST538 and its exopolysaccharide (eps) mutant strains on the innate antiviral immune response triggered by Toll-like receptor 3 (TLR3) activation in porcine intestinal epithelial cells (PIE cells).…”