Our work provides further characterization of the anti-allergic effects of probiotic LAB strains, and identifies new targets for preventive and curative treatment of food allergies. Introduction Th2-regulated immune responses can be induced by food allergens, characterized by activation of mast cells or basophils and production of food protein-specific immunoglobulin E (IgE) resulting in the development of food hypersensitivity reactions1. CD4+Foxp3+Tregs in combination with IL-10 producing. Bc-specific induction of CD4+Foxp3+ Tregs also suppresses Th17 pro-inflammatory response in this mouse model. Finally, the intake of Bc suppresses mTOR activation and thus the phosphorylation of downstream factors. Inhibition of mTOR signaling by Bc further results in FOXP3 up-regulation and GATA-3 down-regulation, which, in turn, facilitate to control Th2-predominant and Th17 pro-inflammatory responses caused by ST. Our work provides further characterization of the anti-allergic effects of probiotic LAB strains, and identifies new targets for preventive and curative treatment of food allergies. Introduction Th2-regulated immune responses can be induced by food allergens, characterized by activation of mast cells or basophils and production of food protein-specific immunoglobulin E (IgE) resulting in the development of food hypersensitivity reactions1. IgE-mediated food allergy has been estimated to affect 1C2% of the adult population and up to 5C8% of children2 and has shown an increasing trend in several regions worldwide3. Among food allergies, seafood allergy represents a major concern as it is usually frequently associated with severe anaphylaxis and life-threatening reactions, with fish and shellfish being two of Verteporfin the big eight categories of food allergens4. Shrimp tropomyosin (ST) is the major heat-stable shrimp allergen and accounts for most of the allergenic activity of whole shrimp extract5C7. Recently, experimental and clinical evidence supporting the efficacy of probiotic bacteria in the treatment of gastrointestinal disorders and allergic symptoms has brought on strong interest in the identification of novel strains and characterization of biological mechanisms Verteporfin behind the beneficial effects8C13. Probiotics, which could be introduced in natural host microbial communities, have a positive effect on health that contributes to nutritional physiology, modulation of inflammatory and hypersensitivity responses, or prevention of intestinal infections14, 15. However, results of clinical studies around the efficacy of prophylactic or therapeutic treatments with different bacterial strains in the context of allergic sensitization have been conflicting16C18, and the anti-allergic effects of probiotic bacteria are still not completely defined. Thus, many questions remain unanswered, Verteporfin such as which probiotic strains are the most effective in modulation of allergic responses Verteporfin and how orally administered probiotics affect the systemic immune system19. In the original dogma of possible mechanism of their protective action, it was thought that probiotic bacteria can regulate the Th1/Th2 balance, and mainly induce Th1, thereby skewing the Verteporfin balance away from the Th2 cells that have an important role in allergic inflammation20. In recent years, the original role of probiotics in Th1/Th2 balance has now been expanded to include the induction and balance of additional Th cell subsets, such as Th921, Th1722 and Foxp3+ regulatory T (Treg) cells10, 23C25. It has been proven that administration of a mixture of five probiotic strains mainly induces generation of CD4+Foxp3+ Tregs and increases the suppressor activity of naturally occurring CD4+CD25+ Tregs, which is usually directly mediated by regulatory dendritic cells (rDCs)25. However, it is unlikely that all probiotic bacteria are equally effective in inducing T regulatory cells 09.712, 08.923 and 11.322 displayed an capacity of inducing higher levels of IFN- and lower levels of IL-4 and IL-13 in macrophage-like THP-1 cells. The purpose of the present study was to examine the immunomodulatory capacity of oral administering these three strains in comparison to two commercial LAB strains (CGMCC 1.3724 and CGMCC 1.2471) on Th2 inflammation and anaphylaxis in a mouse model of food allergy to ST. CLU Moreover, we sought to identify the potential molecular mechanism responsible for the preferential induction of CD4+Foxp3+ Tregs and improved balance of T cell subsets by the potent anti-allergic strain. Our results suggest that Treg cells and mTOR might be the useful targets in regulating food allergic responses. Results Different LAB strains exhibit individual protective effect against allergic reactions in ST-sensitized mice To build up a mouse style of shrimp tropomyosin hypersensitivity, BALB/c mice had been.