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Front Cell Infect Microbiol. 2018 Jun 26;8:220. doi: 10.3389/fcimb.2018.00220. eCollection 2018.

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

Guo M1,2, Li R1,2, Xiao Q1, Fan X1, Li N1,2, Shang Y1, Wei L1,2, Chai T1.

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Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Sino-German Cooperative Research Centre for Zoonosis of Animal Origin of Shandong Province, Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China.
Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, Taishan Medical University, Tai'an, China.


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.


EHEC; NF-κB; NOD2; antibacterial ability; rabbits

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