• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Hyperinduction of Host Beta Interferon by a Listeria monocytogenes Strain Naturally Overexpressing the Multidrug Efflux Pump MdrT
【24h】

Hyperinduction of Host Beta Interferon by a Listeria monocytogenes Strain Naturally Overexpressing the Multidrug Efflux Pump MdrT

机译：单核细胞增生性李斯特菌菌株自然诱导过表达多药外排泵MdrT的宿主β干扰素的超诱导。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Many pathogens regulate or modify their immune-stimulating ligands to avoid detection by their infected hosts. Listeria monocytogenes, a facultative intracellular bacterial pathogen, interacts with multiple components of mammalian innate immunity during its infection cycle. During replication within the cytosol of infected cells, L. monocytogenes utilizes two multidrug efflux pumps, MdrM and MdrT, to secrete the small nucleic acid second messenger cyclic-di-AMP (c-di-AMP). Host recognition of c-di-AMP triggers the production of type I interferons, including beta interferon (IFN-β), which, surprisingly, promote L. monocytogenes virulence. In this study, we have examined the capacity of multiple laboratory and clinical isolates of L. monocytogenes to stimulate host production of IFN-β. We have identified the L. monocytogenes strain LO28 as able to hyperinduce IFN-β production in infected cells ～30-fold more than the common laboratory clone L. monocytogenes strain 10403S. Genomic analyses determined that LO28 contains a naturally occurring loss-of-function allele of the transcriptional regulator BrtA and correspondingly derepresses expression of MdrT. Surprisingly, while derepression of MdrT resulted in hyperstimulation of IFN-β, it results in significant attenuation in multiple mouse models of infection. While type I interferons may promote L. monocytogenes virulence, this study demonstrates that unregulated expression of the c-di-AMP-secreting efflux pump MdrT significantly restricts virulence in vivo by an unknown mechanism.
机译：许多病原体调节或修饰其免疫刺激配体，以避免被其感染宿主检测到。单核细胞增生李斯特菌是一种兼性的细胞内细菌病原体，在其感染周期中与哺乳动物先天免疫的多种成分相互作用。在感染细胞的细胞质内复制期间，单核细胞增生李斯特菌利用两个多药外排泵MdrM和MdrT分泌小核酸第二信使环-di-AMP（c-di-AMP）。宿主对c-di-AMP的识别触发了I型干扰素的产生，包括β干扰素（IFN-β），这令人惊讶地促进了单核细胞增生李斯特菌的毒力。在这项研究中，我们检查了单核细胞增生李斯特菌的多种实验室和临床分离株刺激IFN-β宿主产生的能力。我们已经确定，单核细胞增生李斯特氏菌菌株LO28能够比普通实验室克隆单核细胞增生李斯特氏菌菌株10403S高诱导约30倍的感染细胞中的IFN-β产生。基因组分析确定LO28包含转录调节子BrtA的天然功能缺失等位基因，并相应地抑制MdrT的表达。出人意料的是，虽然MdrT的抑制导致IFN-β的过度刺激，但在多种感染小鼠模型中却导致显着的减弱。虽然I型干扰素可能会增强单核细胞增生李斯特菌的毒力，但这项研究表明，分泌c-di-AMP的外排泵MdrT的不受调控的表达通过未知的机制显着限制了体内的毒力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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