本文主要研究内容
作者胡海（2019）在《布鲁菌感染巨噬细胞免疫关键分子的鉴定及其分子机制研究》一文中研究指出：布鲁菌病是由布鲁菌感染引起的人畜共患细菌性传染病,感染后主要引起动物流产和人的波状热。布鲁菌感染宿主细胞后能通过多种方式逃逸宿主的免疫反应,从而在宿主细胞内建立长期持续性的感染。阐明布鲁菌逃逸宿主免疫的机制对于进一步防控布鲁菌病具有重要意义。本研究通过对布鲁菌感染的巨噬细胞不同时间点进行转录组测序,构建了布鲁菌感染巨噬细胞后相关免疫分子动态表达变化,进一步用荧光定量PCR进行验证,鉴定到多个免疫关键分子,选取其中3个重要分子进行研究,从不同宿主分子的角度阐述布鲁菌逃逸免疫的新机制。布鲁菌感染巨噬细胞后期能下调表达TXNIP基因,进一步验证发现布鲁菌感染能够下调表达TXNIP蛋白,其下调表达依赖于活菌以及布鲁菌的IV型分泌系统,在细胞内则通过一氧化氮(NO)来调控TXNIP的表达,而抑制NO的表达后能明显恢复TXNIP的表达。NO的产生也依赖于布鲁菌的IV型分泌系统。说明布鲁菌通过IV型分泌系统影响NO的产生进而调控TXNIP的表达。敲除TXNIP基因后布鲁菌的胞内存活显著提高,进一步研究发现,布鲁菌通过减少活性氧和NO的产生来减弱巨噬细胞的杀伤作用,以利于其胞内存活。布鲁菌感染骨髓来源的巨噬细胞(BMDM)后也发现TXNIP蛋白呈下调表达,在BMDM细胞中干扰TXNIP表达后,也能增强布鲁菌的胞内存活。进一步布鲁菌感染小鼠实验结果表明,TXNIP蛋白也呈现下调表达。表明布鲁菌可能利用相同的机制来有利于其在宿主体内的存活。布鲁菌感染巨噬细胞后能够上调表达HO-1蛋白,并且通过其脂多糖来调节HO-1表达,在细胞内则通过信号通路AMPK/GSK3β,AKT/GSK3β来调控HO-1蛋白的表达,抑制AMPK,PI3K通路后能减弱HO-1的表达。而缺失Nrf2表达后,也能明显减弱HO-1的表达。说明在细胞内能通过AMPK/GSK3β,AKT/GSK3β和Nrf2共同来调节HO-1的表达。敲除HO-1和Nrf2基因后布鲁菌胞内存活明显减弱。在BMDM细胞和小鼠实验结果也发现布鲁菌感染后HO-1呈上调表达,且布鲁菌上调HO-1蛋白表达能有利于其在BMDM中存活。因此,布鲁菌能够通过上调表达HO-1来利于其胞内存活。布鲁菌感染巨噬细胞后能够上调表达Prdx5蛋白,并且通过其脂多糖来调节Prdx5表达,敲除Prdx5基因后布鲁菌胞内存活明显减弱。进一步研究发现布鲁菌能通过上调表达Prdx5的表达来减弱活性氧和NO的产生来增强布鲁菌的胞内存活。在BMDM细胞和小鼠实验结果也发现布鲁菌感染后Prdx5呈上调表达。因此,布鲁菌能够通过上调表达蛋白Prdx5来有利于其胞内存活。综上所述,本研究通过布鲁菌感染巨噬细胞转录组测序,鉴定到多个布鲁菌逃逸宿主免疫的关键基因,进一步对其中TXNIP,HMOX1,Prdx5基因研究,初步阐述了这些宿主因子在布鲁菌逃逸免疫中所发挥的作用,从不同的角度阐释了布鲁菌逃逸宿主免疫的新机制,为进一步防控布鲁菌病提供了理论基础。
Abstract
bu lu jun bing shi you bu lu jun gan ran yin qi de ren chu gong huan xi jun xing chuan ran bing ,gan ran hou zhu yao yin qi dong wu liu chan he ren de bo zhuang re 。bu lu jun gan ran su zhu xi bao hou neng tong guo duo chong fang shi tao yi su zhu de mian yi fan ying ,cong er zai su zhu xi bao nei jian li chang ji chi xu xing de gan ran 。chan ming bu lu jun tao yi su zhu mian yi de ji zhi dui yu jin yi bu fang kong bu lu jun bing ju you chong yao yi yi 。ben yan jiu tong guo dui bu lu jun gan ran de ju shi xi bao bu tong shi jian dian jin hang zhuai lu zu ce xu ,gou jian le bu lu jun gan ran ju shi xi bao hou xiang guan mian yi fen zi dong tai biao da bian hua ,jin yi bu yong ying guang ding liang PCRjin hang yan zheng ,jian ding dao duo ge mian yi guan jian fen zi ,shua qu ji zhong 3ge chong yao fen zi jin hang yan jiu ,cong bu tong su zhu fen zi de jiao du chan shu bu lu jun tao yi mian yi de xin ji zhi 。bu lu jun gan ran ju shi xi bao hou ji neng xia diao biao da TXNIPji yin ,jin yi bu yan zheng fa xian bu lu jun gan ran neng gou xia diao biao da TXNIPdan bai ,ji xia diao biao da yi lai yu huo jun yi ji bu lu jun de IVxing fen bi ji tong ,zai xi bao nei ze tong guo yi yang hua dan (NO)lai diao kong TXNIPde biao da ,er yi zhi NOde biao da hou neng ming xian hui fu TXNIPde biao da 。NOde chan sheng ye yi lai yu bu lu jun de IVxing fen bi ji tong 。shui ming bu lu jun tong guo IVxing fen bi ji tong ying xiang NOde chan sheng jin er diao kong TXNIPde biao da 。qiao chu TXNIPji yin hou bu lu jun de bao nei cun huo xian zhe di gao ,jin yi bu yan jiu fa xian ,bu lu jun tong guo jian shao huo xing yang he NOde chan sheng lai jian ruo ju shi xi bao de sha shang zuo yong ,yi li yu ji bao nei cun huo 。bu lu jun gan ran gu sui lai yuan de ju shi xi bao (BMDM)hou ye fa xian TXNIPdan bai cheng xia diao biao da ,zai BMDMxi bao zhong gan rao TXNIPbiao da hou ,ye neng zeng jiang bu lu jun de bao nei cun huo 。jin yi bu bu lu jun gan ran xiao shu shi yan jie guo biao ming ,TXNIPdan bai ye cheng xian xia diao biao da 。biao ming bu lu jun ke neng li yong xiang tong de ji zhi lai you li yu ji zai su zhu ti nei de cun huo 。bu lu jun gan ran ju shi xi bao hou neng gou shang diao biao da HO-1dan bai ,bing ju tong guo ji zhi duo tang lai diao jie HO-1biao da ,zai xi bao nei ze tong guo xin hao tong lu AMPK/GSK3β,AKT/GSK3βlai diao kong HO-1dan bai de biao da ,yi zhi AMPK,PI3Ktong lu hou neng jian ruo HO-1de biao da 。er que shi Nrf2biao da hou ,ye neng ming xian jian ruo HO-1de biao da 。shui ming zai xi bao nei neng tong guo AMPK/GSK3β,AKT/GSK3βhe Nrf2gong tong lai diao jie HO-1de biao da 。qiao chu HO-1he Nrf2ji yin hou bu lu jun bao nei cun huo ming xian jian ruo 。zai BMDMxi bao he xiao shu shi yan jie guo ye fa xian bu lu jun gan ran hou HO-1cheng shang diao biao da ,ju bu lu jun shang diao HO-1dan bai biao da neng you li yu ji zai BMDMzhong cun huo 。yin ci ,bu lu jun neng gou tong guo shang diao biao da HO-1lai li yu ji bao nei cun huo 。bu lu jun gan ran ju shi xi bao hou neng gou shang diao biao da Prdx5dan bai ,bing ju tong guo ji zhi duo tang lai diao jie Prdx5biao da ,qiao chu Prdx5ji yin hou bu lu jun bao nei cun huo ming xian jian ruo 。jin yi bu yan jiu fa xian bu lu jun neng tong guo shang diao biao da Prdx5de biao da lai jian ruo huo xing yang he NOde chan sheng lai zeng jiang bu lu jun de bao nei cun huo 。zai BMDMxi bao he xiao shu shi yan jie guo ye fa xian bu lu jun gan ran hou Prdx5cheng shang diao biao da 。yin ci ,bu lu jun neng gou tong guo shang diao biao da dan bai Prdx5lai you li yu ji bao nei cun huo 。zeng shang suo shu ,ben yan jiu tong guo bu lu jun gan ran ju shi xi bao zhuai lu zu ce xu ,jian ding dao duo ge bu lu jun tao yi su zhu mian yi de guan jian ji yin ,jin yi bu dui ji zhong TXNIP,HMOX1,Prdx5ji yin yan jiu ,chu bu chan shu le zhe xie su zhu yin zi zai bu lu jun tao yi mian yi zhong suo fa hui de zuo yong ,cong bu tong de jiao du chan shi le bu lu jun tao yi su zhu mian yi de xin ji zhi ,wei jin yi bu fang kong bu lu jun bing di gong le li lun ji chu 。
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论文详细介绍
论文作者分别是来自中国农业科学院的胡海，发表于刊物中国农业科学院2019-07-05论文，是一篇关于布鲁菌论文,逃逸免疫论文,型分泌系统论文,脂多糖论文,活性氧论文,中国农业科学院2019-07-05论文的文章。本文可供学术参考使用，各位学者可以免费参考阅读下载，文章观点不代表本站观点，资料来自中国农业科学院2019-07-05论文网站，若本站收录的文献无意侵犯了您的著作版权，请联系我们删除。
标签：布鲁菌论文; 逃逸免疫论文; 型分泌系统论文; 脂多糖论文; 活性氧论文; 中国农业科学院2019-07-05论文;