Paraimmunobiotic Bifidobacteria Modulate the Expression Patterns of Peptidoglycan Recognition Proteins in Porcine Intestinal Epitheliocytes and Antigen Presenting Cells.

Wakako Ikeda-Ohtsubo,Md Aminul Islam,Masanori Tohno,Hisakazu Kobayashi,Hikaru Iida,Leonardo Albarracin,Ayako Miyazaki,Julio Villena,Yoshihito Suda,Haruki Kitazawa,Hisashi Aso,Akm Humayun Kober,Noriyuki Iwabuchi,Hirohide Uenishi,Jin-Zhong Xiao,Tomonori Nochi,Nana Sato

doi:10.3390/cells8080891

Abstract

Peptidoglycan recognition proteins (PGLYRPs) are a family of pattern recognition receptors (PRRs) that are able to induce innate immune responses through their binding to peptidoglycan (PGN), lipopolysaccharide, or lipoteichoic acid, or by interacting with other PRR-ligands. Recently, progress has been made in understanding the immunobiology of PGLYRPs in human and mice, however, their functions in livestock animals have been less explored. In this study, we characterized the expression patterns of PGLYRPs in porcine intestinal epithelial (PIE) cells and antigen-presenting cells (APCs) and their modulation by the interactions of host cells with PRR-ligands and non-viable immunomodulatory probiotics referred to as paraimmunobiotics. We demonstrated that PGLYRP-1, -2, -3, and -4 are expressed in PIE cells and APCs from Peyer’s patches, being PGLYPR-3 and -4 levels higher than PGLYRP-1 and -2. We also showed that PGLYRPs expression in APCs and PIE cells can be modulated by different PRR agonists. By using knockdown PIE cells for TLR2, TLR4, NOD1, and NOD2, or the four PGLYRPs, we demonstrated that PGLYRPs expressions would be required for activation and functioning of TLR2, TLR4, NOD1, and NOD2 in porcine epitheliocytes, but PGLYRPs activation would be independent of those PRR expressions. Importantly, we reported for the first time that PGLYRPs expression can be differentially modulated by paraimmunobiotic bifidobacteria in a strain-dependent manner. These results provide evidence for the use of paraimmunobiotic bifidobacteria as an alternative for the improvement of resistance to intestinal infections or as therapeutic tools for the reduction of the severity of inflammatory damage in diseases in which a role of PGLYRPs-microbe interaction has been demonstrated.

Highlights

The innate immune system provides the first line of defense against invading microorganisms employing different strategies to discriminate non-self-structures from self-molecules
Our results suggest that NOD2 would be involved, at least partially, in the regulatory effect of bifidobacteria in Peptidoglycan recognition proteins (PGLYRPs) expressions since the NOD2 agonist was the only pattern recognition receptors (PRRs) ligand able to increase the expression of the four PGLYRPs in a similar trend as bifidobacteria
We showed in this work for the first time the expression patterns of PGLYRP-1, PGLYRP-2, PGLYRP-3, and PGLYRP-4 in porcine IECs and antigen-presenting cells (APCs), and the modulation of their expression by PRRs ligands

Summary

Introduction

The innate immune system provides the first line of defense against invading microorganisms employing different strategies to discriminate non-self-structures from self-molecules. This function is mediated by germ-line encoding pattern recognition molecules called pattern recognition receptors (PRRs) that recognize the conserved pathogen-associated molecular patterns (PAMPs) present in microorganisms but absent in the host, such as lipopolysaccharides (LPS) of Gram-negative bacteria, lipoteichoic acids (LTA) of Gram-positive bacteria or peptidoglycan (PGN) of both Gram-positive and -negative bacteria [1]. PGN and its fragments are primarily recognized by peptidoglycan recognition proteins (PGLYRPs or PGRPs), a novel family of PRR, which were initially named according to their ability to bind PGN [3,4]. PGLYRPs can sense the ligands of other PRRs including toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-containing proteins [2,5]

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