Suppression of NF-κB activation and proinflammatory cytokine expression by Shiga toxin-producing Escherichia coli
Suppression of NF-κB activation and proinflammatory cytokine expression by Shiga toxin-producing Escherichia coli
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DOI：
10.4049/jimmunol.170.4.2074
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发表时间：
2003-02-15
影响因子：
4.4
通讯作者：
Chakraborty, T
中科院分区：
文献类型：
--
作者：
Hauf, N;Chakraborty, T
NF-κ B转录因子家族通过诱导参与炎症和免疫应答的基因的表达形成对抗感染性疾病的第一道防线之一。在这项研究中，我们分析了滋贺毒素产生大肠杆菌（STEC）对HeLa细胞中NF-κ B DNA结合活性的影响。经过一段时间的弱的初始激活，NF-κ B的DNA结合被活的、E.大肠杆菌分泌蛋白B（EspB）的STEC。使用缺乏EspB的同基因突变体或在允许细菌附着后基于庆大霉素杀死STEC后观察到持续的NF-κ B活性。这些观察结果表明，STEC引起NF-κ B活化的能力受到易位的细菌效应蛋白的抑制，所述细菌效应蛋白是EspB本身或需要EspB递送到宿主细胞中。我们发现STEC，肠出血性大肠杆菌。大肠杆菌和肠致病性大肠杆菌。大肠杆菌都干扰由TNF-α启动的NF-κ B活化，表明信号诱导的NF-κ B活性抑制是几种附着和消失细菌的共同特性。作为NF-κ B抑制的结果，与缺乏EspB的细菌相比，野生型STEC在延长的感染期后诱导显著较低的IL-8、IL-6和IL-1 α mRNA水平。对于IL-8和IL-6，抑制作用也反映在细胞因子分泌水平上。通过附着和消除诱导细菌抑制基础和信号诱导的NF-κ B DNA结合似乎是抵消宿主防御反应的积极策略，从而有利于这些病原体的肠道定植。
The NF-kappaB family of transcription factors forms one of the first lines of defense against infectious disease by inducing the expression of genes involved in inflammatory and immune responses. In this study, we analyzed the impact of Shiga toxin-producing Escherichia coli (STEC) on the NF-kappaB DNA-binding activity in HeLa cells. After a period of weak initial activation, DNA binding of NF-kappaB was actively suppressed by viable, E. coli secreted protein B (EspB)-secreting STEC. Sustained NF-kappaB activity was observed either using an isogenic mutant lacking EspB or after gentamicin-based killing of STEC after allowing bacterial attachment. These observations indicate that the ability of STEC to cause NF-kappaB activation is suppressed by a translocated bacterial effector protein, which is either EspB itself or requires EspB for delivery into the host cell. We found that STEC, enterohemorrhagic E. coli, and enteropathogenic E. coli all interfere with NF-kappaB activation initiated by TNF-alpha, indicating that suppression of signal-induced NF-kappaB activity is a property common to several attaching and effacing bacteria. As a consequence of NF-kappaB suppression, wild-type STEC induces significantly lower mRNA levels of IL-8, IL-6, and IL-1alpha upon prolonged infection periods compared with bacteria lacking EspB. For IL-8 and IL-6, the suppressive effect was also reflected at the level of cytokine secretion. Suppression of both basal and signal-induced NF-kappaB DNA binding by attaching and effacing-inducing bacteria appears to be an active strategy to counteract host defense responses, thus favoring intestinal colonization by these pathogens.