AUTHOR=Albarracin Leonardo , Garcia-Castillo Valeria , Masumizu Yuki , Indo Yuhki , Islam Md Aminul , Suda Yoshihito , Garcia-Cancino Apolinaria , Aso Hisashi , Takahashi Hideki , Kitazawa Haruki , Villena Julio 

TITLE=Efficient Selection of New Immunobiotic Strains With Antiviral Effects in Local and Distal Mucosal Sites by Using Porcine Intestinal Epitheliocytes

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00543

DOI=10.3389/fimmu.2020.00543

ISSN=1664-3224

ABSTRACT=<p>Previously, we evaluated the effect of the immunobiotic strain <italic>Lactobacillus rhamnosus</italic> CRL1505 on the transcriptomic response of porcine intestinal epithelial (PIE) cells triggered by the challenge with the Toll-like receptor 3 (TLR-3) agonist poly(I:C) and successfully identified a group of genes that can be used as prospective biomarkers for the screening of new antiviral immunobiotics. In this work, several strains of lactobacilli were evaluated according to their ability to modulate the expression of <italic>IFN</italic>α, <italic>IFN</italic>β, <italic>RIG1</italic>, <italic>TLR3</italic>, <italic>OAS1</italic>, <italic>RNASEL</italic>, <italic>MX2</italic>, <italic>A20</italic>, <italic>CXCL5, CCL4</italic>, <italic>IL-15</italic>, <italic>SELL</italic>, <italic>SELE</italic>, <italic>EPCAM</italic>, <italic>PTGS2</italic>, <italic>PTEGES</italic>, and <italic>PTGER4</italic> in PIE cells after the stimulation with poly(I:C). Comparative analysis of transcripts variations revealed that one of the studied bacteria, <italic>Lactobacillus plantarum</italic> MPL16, clustered together with the CRL1505 strain, indicating a similar immunomodulatory potential. Two sets of <italic>in vivo</italic> experiments in Balb/c mice were performed to evaluate <italic>L. plantarum</italic> MPL16 immunomodulatory activities. Orally administered MPL16 prior intraperitoneal injection of poly(I:C) significantly reduced the levels of the proinflammatory mediators tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-15 in the intestinal mucosa. In addition, orally administered <italic>L. plantarum</italic> MPL16 prior nasal stimulation with poly(I:C) or respiratory syncytial virus infection significantly decreased the levels of the biochemical markers of lung tissue damage. In addition, reduced levels of the proinflammatory mediators TNF-α, IL-6, and IL-8 were found in MPL16-treated mice. Improved levels of IFN-β and IFN-γ in the respiratory mucosa were observed in mice treated with <italic>L. plantarum</italic> MPL16 when compared to control mice. The immunological changes induced by <italic>L. plantarum</italic> MPL16 were not different from those previously reported for the CRL1505 strain in <italic>in vitro</italic> and <italic>in vivo</italic> studies. The results of this work confirm that new immunobiotic strains with the ability of stimulating both local and distal antiviral immune responses can be efficiently selected by evaluating the expression of biomarkers in PIE cells.</p>