首页> 外文学位 >文献详情
【6h】

Cytoplasmic recognition of Chlamydia muridarum: Beyond toll-like receptors.

机译:衣原体衣原体的细胞质识别:超越收费型受体。

获取原文
¥30

摘要

Fallopian tube pathology resulting from infection with the obligate intracellular human pathogen Chlamydia trachomatis has been proposed to be caused by excessive host cytokine production. Using the mouse chlamydiae Chlamydia muridarum, this study was undertaken to better understand the mechanistic basis for production of the pathology associated cytokines IFN-P and IL-1 p. Although cytosolic pathogen recognition receptors are crucial for expression of both cytokines, the chlamydial contributions and host proteins involved are distinct. Using a combination of knockout macrophages and RNAi mediated gene silencing, it was determined that IFN-beta expression was TLR independent, requiring chlamydial growth, signaling through the ER protein STING, and the transcription factor IRF3. Cytosolic NOD1 also contributed to maximal IFN-G3, likely by activation of the transcription factor NF-kappaB and p38 MAPK signaling. The role of IRF3, the key transcription factor in IFN-beta induction, was further examined during an in vivo genital infection. In contrast to IFN-beta, activation of IRF3 is ultimately beneficial to the host as its absence leads to exacerbated uterine horn pathology during infection of the mouse female genital tract, suggesting an IFN-beta independent role for IRF3. In contrast to IFN-beta, IL-1beta secretion in primed macrophages was independent of chlamydial entry and growth. Using gene knockout mouse macrophages, it was determined that C. muridarum was capable of activating the inflammasome for subsequent IL-1beta secretion via multiple pathways utilizing the adaptor protein ASC, including cryopyrin and a putative pyrin domain containing protein(s). To further understand the bacterial contribution in host cytokine induction, the role of the chlamydial Type III secretion (T3S) apparatus in the expression of IL-1beta and IFN-beta was addressed. Administration of a T3S antagonist during infection decreased expression of IFN-beta, cxc110, and IL-6. In contrast, IL-1beta secretion occurred independently of the T3S rod sensing inflammasome protein IPAF. However the fact that T3S is present on the chlamydial elementary body in the absence of de novo protein synthesis, suggests it could still play a role, possibly by an alternate T3S dependent inflammasome. These latter studies illustrate that T3S could be a unifying concept in activation of the cytosolic pathways required for IFN-beta and IL-1beta expression.
机译:已经提出,由于感染了专性细胞内人类病原体沙眼衣原体而导致的输卵管病理是由宿主细胞因子的过量生产引起的。使用小鼠衣原体衣原体,是为了更好地了解与病理相关的细胞因子IFN-P和IL-1 p产生的机制基础。尽管胞质病原体识别受体对于两种细胞因子的表达都至关重要,但衣原体的作用和涉及的宿主蛋白却截然不同。结合使用敲除巨噬细胞和RNAi介导的基因沉默,可以确定IFN-β表达是TLR依赖性的,需要衣原体生长,通过ER蛋白STING和转录因子IRF3进行信号传导。胞质NOD1也可能通过转录因子NF-kappaB和p38 MAPK信号传导的激活而产生最大的IFN-G3。在体内生殖器感染期间,进一步检查了IRF3(IFN-β诱导中的关键转录因子)的作用。与IFN-beta相比,IRF3的激活最终对宿主有益,因为它的缺失会导致小鼠雌性生殖道感染期间子宫角病理恶化,提示IFN-beta对IRF3的独立作用。与IFN-β相反,引发的巨噬细胞中IL-1β的分泌与衣原体的进入和生长无关。使用基因敲除小鼠巨噬细胞,已确定muridarum C.能够通过多种途径利用衔接子蛋白ASC激活炎症小体,以通过随后的IL-1beta分泌,包括冻凝蛋白和推定的含吡啶结构域蛋白。为了进一步了解细菌在宿主细胞因子诱导中的作用,研究了衣原体III型分泌(T3S)装置在IL-1beta和IFN-beta表达中的作用。在感染期间给予T3S拮抗剂可降低IFN-beta,cxc110和IL-6的表达。相反,IL-1β分泌独立于T3S杆感测炎性体蛋白IPAF而发生。但是,在没有从头合成蛋白质的情况下,衣原体中存在T3S的事实表明,它仍可能发挥作用,可能是由另一种依赖T3S的炎性体引起的。后面的这些研究表明,T3S可能是激活IFN-beta和IL-1beta表达所需的胞质途径的统一概念。

著录项

  • 作者

    Prantner, Daniel Joseph.;

  • 作者单位

    University of Arkansas for Medical Sciences.;

  • 授予单位 University of Arkansas for Medical Sciences.;
  • 学科 Biology Microbiology.Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 266 p.
  • 总页数 266
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

站内服务
  • 论文查重
  • 论文收录引证报告
  • 文档翻译
  • 文档转换
获取原文

联系方式:18141920177 (微信同号)

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号