Lactic acid bacteria-specific induction of CD4(+)Foxp3(+)T cells ameliorates shrimp tropomyosin-induced allergic response in mice via suppression of mTOR signaling

The beneficial effects of probiotics have been described in allergic sensitization and diseases; however, many questions remain unanswered, such as characteristics of the most effective strains in modulation of allergic responses and how orally administered probiotics affect the systemic immune system. In the present work, oral administration of five lactic acid bacteria strains showed variable effects on protection against the allergic reaction in a mouse model of food allergy to shrimp tropomyosin (ST). The most effective anti-allergic strain, Bacillus coagulans 09.712 (Bc), greatly improved epithelial barrier function and increased lymphocytes proliferation. Moreover, Bc suppresses ST sensitization by altering Th1/Th2/Treg balance as a result of strong induction of 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.