Immunobiotics for the Bovine Host: Their Interaction with Intestinal Epithelial Cells and Their Effect on Antiviral Immunity

Abstract

The scientific community has reported several cases of microbes that exhibit elevated rates of antibiotic resistance in different regions of the planet. Due to this emergence of antimicrobial resistant microorganisms, the use of antibiotics as promoters of livestock animals' growth is being banned in most countries around the world. One of the challenges of agricultural immunology therefore is to find alternatives by modulating the immune system of animals in drug-independent safe food production systems. In this regard, in an effort to supplant antibiotics from bovine feeds, several alternatives were proposed including the use of immunomodulatory probiotics (immunobiotics). The purpose of this review is to provide an update of the status of the modulation of intestinal antiviral innate immunity of the bovine host by immunobiotics, and the beneficial impact of immunobiotics on viral infections, focused on intestinal epithelial cells (IECs). The results of our group, which demonstrate the capacity of immunobiotic strains to beneficially modulate Toll-like receptor 3-triggered immune responses in bovine IECs and improve the resistance to viral infections, are highlighted. This review provides comprehensive information on the innate immune response of bovine IECs against virus, which can be further investigated for the development of strategies aimed to improve defenses in the bovine host.

Keywords: agricultural immunology; antiviral immunity; beneficial microbes; bovine rotavirus; immunobiotics; inflammation; toll-like receptor 3 pathway.

Figure 1

Antiviral Innate immune response against rotavirus in bovine intestinal epithelial (BIE) cells. Rotavirus double-stranded genomic RNA activates toll-like receptor 3 (TLR3), retinoic acid inducible gene-I (RIG-I), and melanoma differentiation-associated gene-5 (MDA-5), which are pattern recognition receptors (PRRs) expressed in BIE cells. Cellular signaling cascades are activated and converge at the level of interferon (IFN) regulatory factor-3 (IRF3) that upregulate the expression of type I (IFN-α, IFN-β) and type III (IFNλ1, IFNλ2/3) IFN, which in turn induces the synthesis of IFN-stimulated genes with antiviral activities including: myxovirus resistance 1 IFN-inducible protein (Mx1), MxA, ribonuclease L (RNaseL), 2′-5′-oligoadenylate synthetase (OAS), and protein kinase R (PKR). Antiviral PRRs also activate nuclear factor κB (NF-κB) pathway and induce the secretion of proinflammatory cytokines and chemokines including: interleukin 6 (IL-6), IL-8, monocyte chemotactic protein 1 (MCP-1/CCL2), and IFN gamma-induced protein 10 (IP-10/CXCL10).

Figure 2

Beneficial effects of immunobiotics on the antiviral innate immune response against rotavirus in bovine intestinal epithelial (BIE) cells. Rotavirus doublestranded genomic RNA activates toll-like receptor 3 (TLR3), retinoic acid inducible gene-I (RIG-I), and melanoma differentiation-associated gene-5 (MDA-5), which are pattern recognition receptors (PRRs) expressed in IECs. Cellular signaling cascades mediated by interferon (IFN) regulatory factor-3 (IRF3) upregulate the expression of type I (IFN-α, IFN-β), and type III (IFNλ1, IFNλ2/3) IFN, which in turn induces the synthesis of IFN-stimulated genes with antiviral activities including: myxovirus resistance 1 IFN-inducible protein (Mx1), MxA, ribonuclease L (RNaseL), 2′-5′-oligoadenylate synthetase (OAS), and protein kinase R (PKR). Antiviral PRRs also activate nuclear factor κB (NF-κB) pathway and induce the secretion of proinflammatory cytokines and chemokines including: interleukin 6 (IL-6), IL-8, monocyte chemotactic protein 1 (MCP-1/CCL2), and IFN gamma-induced protein 10 (IP-10/CXCL10). Preventive treatment of BIE cells with immunobiotics increase the activation of IRF3, improve the production of the antiviral factors and differentially regulate the expression of inflammatory mediators.