Intestinal barrier: A gentlemen’s agreement between microbiota and immunity

Figure 3 Pathways involved in the improvement and in the impairment of the intestinal barrier. Some probiotic molecules seem to modulate changes in host cell signaling, such as the p40 and p75 proteins, which comodulate phosphoinositide 3-kinase (PI3K)/Akt signaling. When tumor necrosis factor-α (TNF-α), interleukin (IL)-1α and interferon (IFN)-γ are secreted, the p40 protein and unidentified epidermal growth factor receptor (EGFR) ligands stimulate the production of Bcl2, stabilizing tight junctions and promoting epithelial barrier function and cell survival. Toll-like receptor (TLR) and NOD-like receptor (NLR) signaling triggered by microbe-associated molecular patterns (MAMPs) are likely to have roles in the production of physical and chemical defenses in the small intestine, limiting numbers of mucosa-associated bacteria and preventing bacterial penetration of host tissues. Moreover, BCL-9, ERK3, JUN and poly(ADP-ribose) polymerase (PARP)14 have also been implicated in the signaling events induced by probiotics, leading to induction of IFN/STAT4 pathway activation and to the production of T helper 1-type cytokines. On the other hand, evidences suggest that the mast cell tryptase is involved in the degradation of the tight-junction proteins and increased permeability, since the infiltration and activation of these cells are increased in inflammatory bowel syndrom patients in association with higher output of tryptase from their mucosal biopsies. BCL9: B-cell lymphoma-9; JNK: c-Jun N-Terminal Protein Kinase; ERK: Extracellular signal-regulated kinase.