Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
PLoS Pathog. 2010 Jan 29;6(1):e1000743. doi: 10.1371/journal.ppat.1000743.
The complex host-pathogen interplay involves the recognition of the pathogen by the host's innate immune system and countermeasures taken by the pathogen. Detection of invading bacteria by the host leads to rapid activation of the transcription factor NF-kappaB, followed by inflammation and eradication of the intruders. In response, some pathogens, including enteropathogenic Escherichia coli (EPEC), acquired means of blocking NF-kappaB activation. We show that inhibition of NF-kappaB activation by EPEC involves the injection of NleE into the host cell. Importantly, we show that NleE inhibits NF-kappaB activation by preventing activation of IKKbeta and consequently the degradation of the NF-kappaB inhibitor, IkappaB. This NleE activity is enhanced by, but is not dependent on, a second injected effector, NleB. In conclusion, this study describes two effectors, NleB and NleE, with no similarity to other known proteins, used by pathogens to manipulate NF-kappaB signaling pathways.
宿主-病原体的复杂相互作用涉及宿主固有免疫系统对病原体的识别以及病原体采取的对策。宿主检测到入侵的细菌会导致转录因子 NF-κB 的迅速激活，随后引发炎症并清除入侵者。作为回应，包括肠致病性大肠杆菌（EPEC）在内的一些病原体获得了阻止 NF-κB 激活的手段。我们发现，EPEC 通过将 NleE 注入宿主细胞来抑制 NF-κB 的激活。重要的是，我们发现 NleE 通过阻止 IKKβ的激活以及随后 NF-κB 抑制剂 IkappaB 的降解来抑制 NF-κB 的激活。这种 NleE 活性通过但不依赖于第二种注入的效应子 NleB 得到增强。总之，这项研究描述了两种效应子，NleB 和 NleE，它们与其他已知蛋白没有相似性，被病原体用来操纵 NF-κB 信号通路。
