兔NLRX1在肠出血性大肠杆菌感染中的功能表征及免疫调控机制

Abstract

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.