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

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.

NOD2 silencing promotes cell apoptosis and inhibits drug resistance in chronic lymphocytic leukemia by inhibiting the NF‐κB signaling pathway

“…[ 17–19,29 ] NOD2 significantly activates the NF‐κB signaling pathway and enhances antibacterial defenses, thereby increasing the expression of pro‐inflammatory cytokines and defensins after stimulation with Escherichia coli . [ 24 ] Moreover, in our study, NOD2 silencing or inhibition of the NF‐κB signaling pathway contributes to an elevation in ADR accumulation in CLL cells.…”

“…[ 23 ] NOD2 is presumed to function as an innate immune receptor [ 23 ] and is a significant member of the NOD‐like receptor family, which plays a key role in innate immune responses and innate antibacterial responses. [ 24 ] Although the role of NOD2 in CLL remains unknown, NOD2 deregulation has been shown to result in Crohn's inflammation by inducing changes in the gut microbiome that influence immune effector or regulatory functions. [ 25 ] Additionally, NOD2 is functionally expressed in oral squamous cell carcinoma cells, where it not only regulates innate immune responses but also inhibits proliferation and promotes apoptosis.…”