Lactobacillus delbrueckii CRL 581 Differentially Modulates TLR3-Triggered Antiviral Innate Immune Response in Intestinal Epithelial Cells and Macrophages.

Mariano Elean,Kohtaro Fukuyama,Elvira M Hebert,Shugo Kitahara,Lucila Saavedra,Leonardo Albarracin,Yoshihito Suda,Shota Araki,Haruki Kitazawa,Binghui Zhou,Mikado Tomokiyo,Julio Villena

doi:10.3390/microorganisms9122449

Abstract

Lactobacillus delbrueckii subsp. lactis CRL 581 beneficially modulates the intestinal antiviral innate immune response triggered by the Toll-like receptor 3 (TLR3) agonist poly(I:C) in vivo. This study aimed to characterize further the immunomodulatory properties of the technologically relevant starter culture L. delbrueckii subsp. lactis CRL 581 by evaluating its interaction with intestinal epithelial cells and macrophages in the context of innate immune responses triggered by TLR3. Our results showed that the CRL 581 strain was able to adhere to porcine intestinal epithelial (PIE) cells and mucins. The CRL 581 strain also augmented the expression of antiviral factors (IFN-α, IFN-β, Mx1, OAS1, and OAS2) and reduced inflammatory cytokines in PIE cells triggered by TLR3 stimulation. In addition, the influence of L. delbrueckii subsp. lactis CRL 581 on the response of murine RAW macrophages to the activation of TLR3 was evaluated. The CRL 581 strain was capable of enhancing the expression of IFN-α, IFN-β, IFN-γ, Mx1, OAS1, TNF-α, and IL-1β. Of note, the CRL 581 strain also augmented the expression of IL-10 in macrophages. The results of this study show that the high proteolytic strain L. delbrueckii spp. lactis CRL 581 was able to beneficially modulate the intestinal innate antiviral immune response by regulating the response of both epithelial cells and macrophages relative to TLR3 activation.

Highlights

We demonstrated that L. delbrueckii subsp. lactis CRL 581 beneficially influenced the intestinal antiviral innate immune response since it was able to significantly augment the intestinal levels of IFN-γ and IFN-β in mice and protect against intestinal inflammatory damage after the challenge with the Toll-like receptor 3 (TLR3) agonist poly(I:C) [18]
This study aimed to further characterize the immunomodulatory properties of the technologically relevant starter culture L. delbrueckii subsp. lactis CRL 581 by evaluating its interaction with Intestinal epithelial cells (IECs) and macrophages in the context of the innate immune response triggered by the activation of TLR3
We have demonstrated previously that immunobiotic strains able to diminish the increase in A20 in IECs after viral or poly(I:C) challenges could help to enhance the innate immune response mediated by IFNs [22,23,30,41]

Summary

Introduction

Diarrhea and gastroenteritis caused by rotavirus is one of the most important causes of hospitalization and mortality in children. The mortality and morbidity associated with rotavirus infection in infants was diminished in recent years by vaccine applications, such intestinal infection is still a persistent problem globally. It is estimated that at least 200,000 young children die of diarrhea annually due to the severe infections produced by this virus [1,2,3]. Intestinal epithelial cells (IECs) located in the villi of the small intestine are the main target of rotavirus, and its replication induces villous blunting

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