Bifidobacterium breve MCC-117 induces tolerance in porcine intestinal epithelial cells: study of the mechanisms involved in the immunoregulatory effect

KOZUE MURATA; YOHSUKE TOMOSADA; JULIO VILLENA; ERIKO CHIBA; TOMOYUKI SHIMAZU; HISASHI ASO; YOSHIHITO SUDA; NORIYUKI IWABUCHI; JIN-ZHONG XIAO; TADAO SAITO; HARUKI KITAZAWA

Bioscience of the Microbiota Food Helath

BMFH Press

Lugar: Tokyo; Año: 2014

2186-6953

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 the observed for the MCC-117 strain. Considering the different capacity of both bifidobacteria 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 TLRs negative regulators as well as the inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMPs-induced NF-κB, p38 MAPK and PI3K 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 receptor (PRR), and these interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. The 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 have gained insight in the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117.