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

Linglin Fu,Xiurong Su,Yan Zhang,Yanbo Wang,Shushu Zhao,Jixiang Peng

doi:10.1038/s41598-017-02260-8

Abstract

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.

Highlights

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 reactions[1]
We investigated whether these five different lactic acid bacteria (LAB) strains were able to attenuate food anaphylaxis in this mouse model when administered by the oral route
The levels of specific IgE (sIgE) and sIgG1 on day 61 were significantly lower (p < 0.05) in mice supplemented for 20 days with daily oral administration of B. coagulans (Bc) and L. plantarum (Lp) compared to the control, while no significant differences from the control were found in B. infantis (Bi), Bt- and L. rhamnosus (Lr)-treated mice (Fig. 2A,B)

Summary

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 reactions[1]. MTORC2 activity leads to the phosphorylation of Akt (at position S473) and SGK1, leading to their activation and in turn resulting in the phosphorylation and sequestration of FOXO proteins in the cytoplasm This prevents the FOXO proteins from activating the transcription of target genes such as foxp[3], a critical modulator of Treg development and function[26, 27]. The knowledge of cellular and molecular mechanisms underlying the preferential induction of Treg cell differentiation by probiotic strains involved in anti-allergic response is still incomplete

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