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首页> 外文期刊>Infection and immunity >The p50 Subunit of NF-κB Is Critical for In Vivo Clearance of the Noninvasive Enteric Pathogen Citrobacter rodentium
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The p50 Subunit of NF-κB Is Critical for In Vivo Clearance of the Noninvasive Enteric Pathogen Citrobacter rodentium

机译:NF-κB的p50亚基对于无创性肠病原鼠柠檬酸杆菌的体内清除至关重要

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Citrobacter rodentium, a natural mouse pathogen, belongs to the family of extracellular enteric pathogens that includes enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). C. rodentium shares many virulence factors with EPEC and EHEC and relies on attaching-and-effacing lesion formation for colonization and infection of the gut. In vivo, C. rodentium infection is characterized by increased epithelial cell proliferation, mucosal thickening, and a TH1-type immune response, but with protective immunity believed to be mediated by serum immunoglobulin G (IgG). In this work, we characterize the immune response and pathology of mice lacking the p50 subunit of the transcription factor nuclear factor kappa B (NF-κB) during C. rodentium infection. We show that p50?/? mice are unable to clear C. rodentium infection. Furthermore, these animals show a reduced influx of immune cells into infected colonic tissue and greater levels of mucosal hyperplasia and the cytokines tumor necrosis factor alpha and gamma interferon. Surprisingly, despite being unable to eliminate infection, p50?/? mice showed markedly higher levels of anti-Citrobacter IgG and IgM, suggesting that antibody alone is not responsible for bacterial clearance. These data also demonstrate that non-NF-κB-dependent defenses are insufficient to control C. rodentium infection, and hence, the NF-κB p50 subunit is critical for defense against this noninvasive pathogen.
机译:啮齿类柠檬酸杆菌是一种天然的小鼠病原体,属于细胞外肠道病原体家族,包括肠致病性大肠杆菌(EPEC)和肠出血性 E。大肠杆菌(EHEC)。 C。啮齿动物与EPEC和EHEC共享许多毒力因子,并依靠附着和破坏的病灶形成来定居和感染肠道。在体内,C。啮齿类动物感染的特征是上皮细胞增殖增加,粘膜增厚和TH1型免疫反应,但据认为具有保护性免疫作用,是由血清免疫球蛋白G(IgG)介导的。在这项工作中,我们表征了在 C期间缺少转录因子核因子κB(NF-κB)p50亚基的小鼠的免疫应答和病理学。啮齿动物感染。我们显示p50 ?/?小鼠无法清除 C。啮齿动物感染。此外,这些动物的免疫细胞向感染的结肠组织的流入减少,并且粘膜增生和细胞因子肿瘤坏死因子α和γ干扰素水平更高。出人意料的是,尽管不能消除感染,但p50 ?/?小鼠显示出明显更高的抗- IgG和IgM水平,表明单独的抗体与细菌清除无关。这些数据还表明,非NF-κB依赖性防御不足以控制C。啮齿类动物感染,因此NF-κBp50亚基对于防御这种非侵入性病原体至关重要。

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