<i>Bifidobacterium breve</i> MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

Abstract

Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4+CD25high Foxp3+ lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117.

The toll-like receptor family protein RP105/MD1 complex is involved in the immunoregulatory effect of exopolysaccharides from Lactobacillus plantarum N14

“…More recently, Finamore et al (2014) signaling in Caco-2/TC7 cells through modulation of the negative regulators Tollip and IRAK-M and, that this effect was dependent on TLR2 signaling. Our previous studies in PIE cells and porcine immune cells also revealed that TLR2 plays an important role in the immunoregulatory activity of immunobiotic bacteria (Shimazu et al, 2012;Tomosada et al, 2013;Villena et al, 2012;Murata et al, 2014). Our studies of the anti-inflammatory activity of L. jensenii TL2937 in PIE cells showed that TLR2 have an important role in the immunoregulatory capacities of this strain.…”

Lactobacillus delbrueckiiTUA4408L and its extracellular polysaccharides attenuate enterotoxigenic Escherichia coli‐induced inflammatory response in porcine intestinal epitheliocytes via Toll‐like receptor‐2 and 4

“…Interestingly, the production of cytokines and chemokines in response to ETEC PAMPs by IECs can be modulated with immunobiotic bacteria . In this regard, we have previously demonstrated that L. jensenii TL2937, B. longum BB536, and B. breve MCC‐117 are able to protect PIE cells from ETEC‐mediated inflammatory damage by regulating NF‐κB and MAPK pathways, and suppressing proinflammatory cytokine expression . However, the anti‐inflammatory activity of plant‐derived lactobacilli has been studied to a very limited extent.…”

“…Every year, increasing substantial clinical and experimental evidence is reported to support probiotic intervention in immunomodulation . The beneficial effects of immunobiotic LAB have been demonstrated in several in vitro and in vivo studies, which revealed a variety of host effects and generated several hypotheses of the mechanisms by which immunobiotics influence their hosts . Regarding the immunoregulatory effect of immunobiotics, it is now well established that within the gastrointestinal system, probiotics are capable to interact with the host's epithelial‐ and immune cells, and thereby impact epithelial barrier and immune functions .…”

Immunomodulating effects of probiotics for microbiota modulation, gut health and disease resistance in pigs

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