The molecular mechanism for activating IgA production by Pediococcus acidilactici K15 and the clinical impact in a randomized trial

Tadaomi Kawashima,Yoshiro Kubota,Yasuyuki Kowatari,Naoki Shimojo,Tomoko Kouchi,Noriko M Tsuji,Naho Ikari

doi:10.1038/s41598-018-23404-4

Abstract

IgA secretion at mucosal sites is important for host defence against pathogens as well as maintaining the symbiosis with microorganisms present in the small intestine that affect IgA production. In the present study, we tested the ability of 5 strains of lactic acid bacteria stimulating IgA production, being Pediococcus acidilactici K15 selected as the most effective on inducing this protective immunoglobulin. We found that this response was mainly induced via IL-10, as efficiently as IL-6, secreted by K15-stimulated dendritic cells. Furthermore, bacterial RNA was largely responsible for the induction of these cytokines; double-stranded RNA was a major causative molecule for IL-6 production whereas single-stranded RNA was critical factor for IL-10 production. In a randomized, double-blind, placebo-controlled clinical trial, ingestion of K15 significantly increased the secretory IgA (sIgA) concentration in saliva compared with the basal level observed before this intervention. These results indicate that functional lactic acid bacteria induce IL-6 and IL-10 production by dendritic cells, which contribute to upregulating the sIgA concentration at mucosal sites in humans.

Highlights

A variety of lactic acid bacteria (LAB) from fermented foods or human microbiota show multiple beneficial effects on human health[1,2,3,4]
These results indicate that, in human peripheral blood mononuclear cells (PBMCs), the effects of LAB on activating IgA production are induced by IL-6 and IL-10, most likely secreted by dendritic cells (DCs) in response to LAB
It has been reported that probiotic strains of LAB activate IgA production by B cells; this molecular mechanism was revealed in mice[17]

Summary

Introduction

A variety of lactic acid bacteria (LAB) from fermented foods or human microbiota show multiple beneficial effects on human health[1,2,3,4]. The production of type I interferons (IFNs), IFN-α and IFN-β from dendritic cells (DCs) upon LAB-stimulation were reported beneficial for exerting an anti-viral effect against influenza virus[5,15,16] Another major mechanism of LAB to improve host defence in the gut is enhancement of production in specific antibodies (Ab) against pathogens, and the overall increase in total IgA5,15,17. In addition to antigen/pathogen-specific targeting by immunoglobulin, secretory IgA is equipped with glycan-dependent innate immunity, which protects the gut from pathogen invasion by inhibiting the adherence of diverse and variable mucosal microorganisms, i.e. their glycan-moieties compete with epithelial receptors for pathogens[18] Given that both Ag-specific and non-specific IgA protect mucosal surfaces from pathogen invasion and colonization, the probiotic effect of orally administered LAB to enhance IgA production contributes to repelling pathogens[5,17]. For IgA production in human system IL-10 is as important as IL-6, which has been reported in murine experimental system[17]

Methods

Results

Conclusion