【作者】 曹璐； 武小曼； 聂品； 昌鸣先；

【Author】 CAO lu;WU xiaoman;NIE ping;CHANG mingxian;Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences;

【机构】 淡水生态与生物技术国家重点实验室水生生物研究所中国科学院；

【摘要】 NLRC5是胞浆内模式识别受体NOD样受体家族中的一个重要成员,它除了与其他NLR样受体一样参与天然免疫反应的调控,也被证明可作为MHC-I类基因的转录激活因子,调控MHC-I类基因的表达。尽管有关NLRC5参与调控抗病毒、抗菌免疫反应及诱导I型干扰素的功能逐渐被知晓,但是有关NLRC5剪接异构体在天然免疫中的作用还未有过报道。目前,我们对克隆得到斑马鱼zf NLRC5a和zf NLRC5d两种不同的剪接异构体研究发现:zfNLRC5a和zf NLRC5d均由"外显子跳跃"的剪接方式产生;并且两种zfNLRC5剪接异构体均可被病毒和细菌感染所诱导。对NLRC5剪接异构体的功能探究发现,在SVCV病毒感染实验中,体内体外过表达zf NLRC5d提高宿主抗病毒感染能力,而过表达zf NLRC5a对宿主抗病毒感染能力无影响。细菌感染实验的结果表明:体内体外过表达zfNLRC5a和zfNLRC5d有利于细菌的增殖。总之,zfNLRC5a和zf NLRC5d均参与宿主抗病毒和抗细菌免疫反应的调控,但是两者在功能上存在一定的相似性和差异性。更多还原

【Abstract】 NOD-like receptors(NLRs) are a family of intracellular pattern recognition receptors(PRRs) that play critical roles in innate immunity against pathogens infection. NLRC5, the largest member of NLR family, has been characterized as a regulator of innate immunity and MHC class I expression. Alternative splicing of NLRC5 is only reported in human and zebrafish. However, the function of NLRC5 isoforms in the innate immune responses remains unknown. In the present study, we report the functional characterization of zfNLRC5 a and zfNLRC5 d, two splicing isoforms of zebrafish NLRC5. zfNLRC5 a and zfNLRC5 d are generated by exon skipping. The expression of zfNLRC5 isoform was inducible in response to bacterial and viral infections. During SVCV infection, the in vitro and in vivo studies found that zfNLRC5 d overexpression increased protection against viral infection; however zfNLRC5 a overexpression had no significant effect on antiviral activity. Overexpression of zfNLRC5 isoforms also contributed to negative regulation of antibacterial immune response. All together, these results firstly demonstrate the function of NLRC5 isoforms in antiviral and antibacterial immune responses both in vitro and in vivo.更多还原