Abstract
Lactobacillus rhamnosus CRL1505 and Lactobacillus plantarum CRL1506 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 of IFN-α and IFN-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, and RNASEL) and cytokines/chemokines (IL-1β, IL-6, CCL4, CCL5, and CXCL10) that were significantly increased in lactobacilli-treated PIE cells. Immunobiotics reduced the expression of IL-15 and RAE1 genes that mediate poly(I:C) inflammatory damage. In addition, lactobacilli treatments increased the expression PLA2G4A, PTGES, and PTGS2 that are involved in prostaglandin E2 biosynthesis. L. rhamnosus CRL1505 and L. plantarum CRL1506 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 damage in 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, and PTGER4), 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.
Highlights
In the past decade, research has demonstrated that beneficial microbes with the capacity to modulate the mucosal immune system are a potential alternative to enhance resistance against viral infections
Changes in the immunotranscriptome response in porcine intestinal epithelial (PIE) cells after poly(I:C) stimulation included genes in the following Gene Ontology (GO) Biological Process pathways: “immune system process,” “regulation of defense response,” “cell adhesion,” “innate immune response,” “regulation of viral process,” “cellular response to interferongamma,” and several pathways related to immune cells migration and chemotaxis (Figure 1C)
It is known that intestinal epithelial cells (IECs) senses viral dsRNA through pattern recognition receptors (PRRs) including TLR3, retinoic acid inducible gene-I (RIG-I), and melanoma differentiation associated gene-5 (MDA-5)
Summary
Research has demonstrated that beneficial microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to enhance resistance against viral infections. Several reports have shown that immunobiotic LAB improve protection against enteric viral infections and shorten the duration of diarrhea, reduce the number of episodes, diminish virus shedding, normalize gut permeability, and increase the production of virus-specific antibodies [1,2,3]. It was demonstrated that some immunobiotic strains, when orally administered, are able to increase respiratory defenses and reduce the susceptibility to respiratory viral infections improving virus clearance and diminishing inflammatory-mediated lung tissue damage [4,5,6,7]. The use of immunobiotics to improve the outcome of those viral infections has been proposed In this regard, in a randomized controlled trial conducted by Villena et al [4], the immunobiotic strain Lactobacillus rhamnosus CRL1505 (administered in a yogurt formulation) improved mucosal immunity and reduced the incidence and severity of intestinal and respiratory infection in children. It was demonstrated that these immunomodulatory capacities are strain specific since other immunobiotic strains such as Lactobacillus plantarum CRL1506 exert only local affects after oral administration [5,6,7, 11]
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