Protective Role of Rabbit Nucleotide-Binding Oligomerization Domain-2 (NOD2)-Mediated Signaling Pathway in Resistance to Enterohemorrhagic Escherichia coli Infection.

Ning Li,Qianqian Xiao,Mengjiao Guo,Liangmeng Wei,Xiuxiu Fan,Rong Li,Tongjie Chai,Yingli Shang

doi:10.3389/fcimb.2018.00220

Abstract

Nucleotide-binding oligomerization domain 2 (NOD2), a member of the NOD-like receptors (NLRs) family that is well-known to play a key role in innate immune responses and is involved in innate antibacterial responses. In this study, rabbit NOD2 (rNOD2) was cloned from rabbit kidney (RK) cells. It was distributed in various tissues, and the highest level of rNod2 was detected in spleen. Moreover, the expression of rNod2 was significantly upregulated in the heart, liver, and spleen induced by enterohemorrhagic Escherichia coli (EHEC). Overexpression of rNOD2 induced the expression of pro-inflammatory cytokine, including Il1β, Il6, Ifn-γ, and Tnf, as well as defensins, including Defb124, Defb125, and Defb128 through the nuclear factor (NF)-κB signaling pathway. Furthermore, overexpression of rNOD2 inhibited the growth of EHEC, and knockdown of rNOD2 or inhibition of the NF-κB pathway promoted its replication. In addition, our results suggest that rNOD2 can significantly activate NF-κB signaling and trigger antibacterial defenses to increase the expression of pro-inflammatory cytokine and defensins after stimulation by EHEC. These findings are useful to further understanding the innate immune system of rabbits and providing a new perspective for the prevention of bacterial diseases in rabbits.

Highlights

The innate immune system plays a crucial role in the non-specific immune response, and is essential for triggering the acquired immune response against microbial pathogens
To understand the evolutionary relationship of rabbit NOD2 (rNOD2), phylogenetic tree was generated based on Nucleotide-binding oligomerization domain 2 (NOD2) protein of various species, and rNOD2 belonged to the branch of mammals
Similar results have been observed in newborn swine, the NOD2 expressed in varies tissues with different level, and the highest expression in the mesenteric lymph nodes and spleen (Tohno et al, 2008)

Summary

Introduction

The innate immune system plays a crucial role in the non-specific immune response, and is essential for triggering the acquired immune response against microbial pathogens. NLRs possess neither signal peptides nor transmembrane domains, and they detect PAMPs that reach the cytosol and trigger innate inflammatory responses and antibacterial immune responses (Elinav et al, 2011). Retinoid acid-inducible gene-1-like receptors are intracellular cytosolic sensors and sense viruses (Kawai and Akira, 2006). They can be classified into soluble and transmembrane CLRs. According to molecular structure, they can be classified into soluble and transmembrane CLRs They recognize and take up various antigens, and transmit signals in cells, helping macrophages and dendritic cells to effectively induce innate immunity (Lepenies et al, 2013; Jung et al, 2018)

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Conclusion