title: Transcriptomic Analysis of the Innate Antiviral Immune Response in Porcine Intestinal Epithelial Cells: Influence of Immunobiotic Lactobacilli.
abstract: Lactobacillus rhamnosusCRL1505 andLactobacillus plantarumCRL1506 are immunobiotic strains able to increase protection against viral intestinal infections as demonstrated in animal models and humans. To gain insight into the host-immunobiotic interaction, the transcriptomic response of porcine intestinal epithelial (PIE) cells to the challenge with viral molecular associated pattern poly(I:C) and the changes in the transcriptomic profile induced by the immunobiotics strains CRL1505 and CRL1506 were investigated in this work. By using microarray technology and reverse transcription PCR, we obtained a global overview of the immune genes involved in the innate antiviral immune response in PIE cells. Stimulation of PIE cells with poly(I:C) significantly increased the expression ofIFN-α andIFN-β, several interferon-stimulated genes, cytokines, chemokines, adhesion molecules, and genes involved in prostaglandin biosynthesis. It was also determined that lactobacilli differently modulated immune gene expression in poly(I:C)-challenged PIE cells. Most notable changes were found in antiviral factors (IFN-α,IFN-β,NPLR3, OAS1, OASL, MX2, andRNASEL) and cytokines/chemokines (IL-1β,IL-6, CCL4, CCL5, andCXCL10) that were significantly increased in lactobacilli-treated PIE cells. Immunobiotics reduced the expression ofIL-15andRAE1genes that mediate poly(I:C) inflammatory damage. In addition, lactobacilli treatments increased the expressionPLA2G4A, PTGES, andPTGS2that are involved in prostaglandin E2 biosynthesis. L. rhamnosusCRL1505 andL. plantarumCRL1506 showed quantitative and qualitative differences in their capacities to modulate the innate antiviral immune response in PIE cells, which would explain the higher capacity of the CRL1505 strain when compared to CRL1506 to protect against viral infection and inflammatory damagein vivo. These results provided valuable information for the deeper understanding of the host-immunobiotic interaction and their effect on antiviral immunity. The comprehensive transcriptomic analyses successfully identified a group of genes (IFN-β,RIG1, RNASEL, MX2, A20, IL27, CXCL5, CCL4, PTGES, andPTGER4), which can be used as prospective biomarkers for the screening of new antiviral immunobiotics in PIE cells and for the development of novel functional food and feeds, which may help to prevent viral infections.
authors.affiliation: Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina; Immunobiotics Research Group, Tucuman, Argentina; Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Albarracin
authors.affiliation: Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Iida
authors.affiliation: Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Sato
authors.affiliation: Cell Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Infection Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nochi
authors.affiliation: Cell Biology Laboratory, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Infection Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Aso
authors.affiliation: Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina; Immunobiotics Research Group, Tucuman, Argentina.
authors.forename: Susana
authors.initials: S
authors.lastname: Salva
authors.affiliation: Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina; Immunobiotics Research Group, Tucuman, Argentina.
authors.forename: Susana
authors.initials: S
authors.lastname: Alvarez
authors.affiliation: Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan; Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kitazawa
authors.affiliation: Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina; Immunobiotics Research Group, Tucuman, Argentina; Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Julio
authors.initials: J
authors.lastname: Villena
keywords: Lactobacillus plantarum CRL1506; Lactobacillus rhamnosus CRL1505; TLR3; antiviral response; immunotranscriptomic response; intestinal epithelial cells