Jiangsu Co-Innovation Center for Prevention of Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Jiangsu Co-Innovation Center for Prevention of Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Joint International Research Laboratory of Agriculture & Agri-Product Safety, Yangzhou University (JIRLAAPS), Yangzhou, Jiangsu, China.
Dev Comp Immunol. 2020 May;106:103612. doi: 10.1016/j.dci.2020.103612. Epub 2020 Jan 10.
Nucleotide oligomerization domain (NOD) like receptor X1 (NLRX1) is a member of pattern recognition receptor, which has been linked to viral response, cancer, and inflammatory diseases. In this study, rabbit NLRX1 (rNLRX1) was firstly cloned from RK-13 cells, which protein contained a NACHT domain and seven LRRs. rNLRX1 was widely expressed in tissues of rabbits, and highly increased in liver, spleen, kidney, and colon after infected with enterohemorrhagic Escherichia coli (EHEC). Overexpression of rNLRX1 negatively regulated NF-κB signaling, and impaired the expression of pro-inflammatory cytokines and defensins. Moreover, deficient of rNLRX1 in RK-13 cells was performed to investigate the possible roles of rNLRX1. Upon EHEC stimulation, knockdown of rNLRX1 markedly enhanced NF-κB activation and downstream responsive cytokines (IL1β and TNFα) and β-defensins (DEFB114, DEFB124, and DEFB125). Furthermore, overexpression of rNLRX1 promoted the proliferation of EHEC, whereas knockdown of rNLRX1 inhibited its growth. Our study identified that rNLRX1 acts as a negative regulatory in anti-microbial responses after EHEC infection.
核苷酸寡聚化结构域（NOD）样受体 X1（NLRX1）是模式识别受体的成员，与病毒反应、癌症和炎症性疾病有关。在这项研究中，首次从 RK-13 细胞中克隆了兔 NLRX1（rNLRX1），其蛋白含有 NACHT 结构域和七个 LRRs。rNLRX1 在兔组织中广泛表达，感染肠出血性大肠杆菌（EHEC）后在肝脏、脾脏、肾脏和结肠中高度增加。rNLRX1 的过表达负调节 NF-κB 信号通路，并损害促炎细胞因子和防御素的表达。此外，还进行了 RK-13 细胞中 rNLRX1 的缺失，以研究 rNLRX1 的可能作用。在 EHEC 刺激下，rNLRX1 的敲低显着增强了 NF-κB 激活及其下游反应性细胞因子（IL1β 和 TNFα）和β-防御素（DEFB114、DEFB124 和 DEFB125）的表达。此外，rNLRX1 的过表达促进了 EHEC 的增殖，而 rNLRX1 的敲低抑制了其生长。我们的研究表明，rNLRX1 在 EHEC 感染后作为抗微生物反应的负调节因子发挥作用。
