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Immunobiotic Lactobacillus strains reduce small intestinal injury induced by intraepithelial lymphocytes after Toll-like receptor 3 activation

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Abstract

Objective

Intestinal intraepithelial lymphocytes (IELs) play critical roles in disrupting epithelial homeostasis after Toll-like receptor (TLR)-3 activation with genomic rotavirus dsRNA or the synthetic dsRNA analog poly(I:C). The capacity of immunobiotic Lactobacillus rhamnosus CRL1505 (Lr1505) or Lactobacillus plantarum CRL1506 (Lp1506) to beneficially modulate IELs response after TLR3 activation was investigated in vivo using a mice model.

Results

Intraperitoneal administration of poly(I:C) induced inflammatory-mediated intestinal tissue damage through the increase of inflammatory cells (CD3+NK1.1+, CD3+CD8αα+, CD8αα+NKG2D+) and pro-inflammatory mediators (TNF-α, IL-1β, IFN-γ, IL-15, RAE1, IL-8). Increased expression of intestinal TLR3, MDA5, and RIG-I was also observed after poly(I:C) challenge. Treatment with Lr1505 or Lp1506 prior to TLR3 activation significantly reduced the levels of TNF-α, IL-15, RAE1, and increased serum and intestinal IL-10. Moreover, CD3+NK1.1+, CD3+CD8αα+, and CD8αα+NKG2D+ cells were lower in lactobacilli-treated mice when compared to controls. The immunomodulatory capacities of lactobacilli allowed a significant reduction of intestinal tissue damage.

Conclusions

This work demonstrates the reduction of TLR3-mediated intestinal tissue injury by immunobiotic lactobacilli through the modulation of intraepithelial lymphocytes response. It is a step forward in the understanding of the cellular mechanisms involved in the antiviral capabilities of immunobiotic strains.

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Abbreviations

AST:

Aspartate aminotransferase

APC:

Antigen presenting cells

DC:

Dendritic cells

dsRNA:

Double-stranded RNA

IELs:

Intraepithelial lymphocytes

IECs:

Intestinal epithelial cells

IFN:

Interferon

IL-1:

Interleukin

LAB:

Lactic acid bacteria

LDH:

Lactate dehydrogenase

Lp1506:

Lactobacillus plantarum CRL1506

Lr1505:

Lactobacillus rhamnosus CRL1505

MAMPs:

Microbe-associated molecular patterns

RAE1:

Retinoic acid early inducible-1

RVs:

Rotavirus

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

PIE:

Porcine intestinal epithelial cells

PRRs:

Pattern recognition receptors

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Acknowledgments

This study was supported by a ANPCyT—FONCyT Grant PICT-2013 (No. 3219) to Dr. J. Villena and Grant-in-Aid for Scientific Research (B)(2) (No. 24380146, 16H05019) and Challenging Exploratory Research (No. 23658216, 26660216, 16K15028) from the Japan Society for the Promotion of Science (JSPS) to Dr. H. Kitazawa.

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    Authors and Affiliations

    1. Immunobiotics Research Group, Tucuman, Argentina

      Asuka Tada, Hortensia Zelaya, Patricia Clua, Susana Salva, Susana Alvarez & Julio Villena

    2. Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina

      Asuka Tada, Hortensia Zelaya, Patricia Clua, Susana Salva, Susana Alvarez & Julio Villena

    3. Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan

      Asuka Tada, Haruki Kitazawa & Julio Villena

    4. Livestock Immunology Unit, International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan

      Asuka Tada & Haruki Kitazawa

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    1. Asuka Tada
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    Correspondence to Haruki Kitazawa or Julio Villena.

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    Ethics

    All experiments were carried out in compliance with the Guide for Care and Use of Laboratory Animals and approved by the Ethical Committee of Animal Care at CERELA, Argentina (Protocol Number BIOT-CRL/14).

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    The authors declare that they have no competing interests.

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    Responsible Editor: John Di Battista.

    A. Tada and H. Zelaya contributed equally to this work.

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    Tada, A., Zelaya, H., Clua, P. et al. Immunobiotic Lactobacillus strains reduce small intestinal injury induced by intraepithelial lymphocytes after Toll-like receptor 3 activation. Inflamm. Res. 65, 771–783 (2016). https://doi.org/10.1007/s00011-016-0957-7

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    • DOI: https://doi.org/10.1007/s00011-016-0957-7

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