MODULATION OF SIGNALING PATHWAYS BY PROBIOTICS IN THE GUT MUCOSA

LEMME DUMIT, JOSÉ MARÍA; SAVEDRA, LUCILA; HEBERT, ELVIRA; PERDIGÓN, GABRIELA.; MALDONADO GALDEANO, CAROLINA

Washington

Congreso; ICMI; 2017

Probiotic strains may modulate the gut immune functions and ameliorate diseases. The modes of action by which probiotics exert their beneficial effects are: exclusion or inhibition of pathogens, enhance the epithelial barrier function by the induction of mucus and anti-microbial substances production, enhancement of tight junction functioning, and modulation of host immune responses, resulting in both local and systemic effects. These effects may be achieved by the interaction of probiotic bacteria (cell wall components or probiotic metabolites) with pattern recognition receptors (PRRs) presents on immune and non-immune cells. These receptors are able to recognize microbial-associated molecular patterns (MAMPs) that are ligands expressed on microorganisms. PRRs-MAMPs interaction is a key event in the generation of immune response. The aim of the current study was to determine the signaling pathways and the regulators of Toll-like receptors (TLRs) activation triggered by probiotic interaction with intestinal epithelial cells (IECs) and peritoneal macrophages (MQP).In vitro cultured of IECs isolated from BALB/c mice were treated with: a-NFκB Ab; a-NFκB Ab + Lactobacillus casei CRL431 (Lc431), IL-6 levels were determined in the supernatant by ELISA. BALB/c mice were treats with Lc431 or its cell walls (CW431) and Lactobacillus paracasei CNCM I-1518 (Lp1518) or its CW1518 during 7 or 5 days, respectively. After that, expressing genes (a20, irak-m, mkp-1 and tollip) were determined on IECs and MQP by RT-qPCR.IL-6 levels from IECs showed decreased values after NF-κB antibody treats, and Lc431 supplementation was not able to increase IL-6 production (p.05). Probiotics bacteria and their cell walls were able to increase the expression of genes regulators of TLRs pathways (a20, irak-m, mkp-1 and tollip) in comparison to Salmonella (negative control).Our previous study showed that probiotics bacteria interact with immune and non-immune cells through TLRs (TLR2 and TLR4) and MyD88 a key molecule to signaling pathways. However, TLRs and MyD88 did not show inference in systemic response. We determined that NF-κB pathway was target for probiotic, because they can not restore cytokines production on IECs after NF-κB antibody treatment. At the same time, negative regulators of NF-κB and MAPK were activated after probiotics treatments both IECs and MQP.We propose that probiotics exert their action in immune and non-immune cells through TLRs and activation downstream by NF-κB and MAPK pathways. However, this interaction is modulated by the regulators of the signaling pathways. Thus, probiotics are able to modulate the gut mucosal immune system.