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Retinoid Levels Influence Enterohemorrhagic Escherichia coli Infection and Shiga Toxin 2 Susceptibility in Mice

机译:类维生素A水平影响小鼠大肠埃希氏大肠杆菌感染和志贺毒素2易感性。

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Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that produces Shiga toxin (Stx) and causes hemorrhagic colitis. Under some circumstances, Stx produced within the intestinal tract enters the bloodstream, leading to systemic complications that may cause the potentially fatal hemolytic-uremic syndrome. Although retinoids like vitamin A (VA) and retinoic acid (RA) are beneficial to gut integrity and the immune system, the effect of VA supplementation on gastrointestinal infections of different etiologies has been controversial. Thus, the aim of this work was to study the influence of different VA status on the outcome of an EHEC intestinal infection in mice. We report that VA deficiency worsened the intestinal damage during EHEC infection but simultaneously improved survival. Since death is associated mainly with Stx toxicity, Stx was intravenously inoculated to analyze whether retinoid levels affect Stx susceptibility. Interestingly, while VA-deficient (VA-D) mice were resistant to a lethal dose of Stx2, RA-supplemented mice were more susceptible to it. Given that peripheral blood polymorphonuclear cells (PMNs) are known to potentiate Stx2 toxicity, we studied the influence of retinoid levels on the absolute number and function of PMNs. We found that VA-D mice had decreased PMN numbers and a diminished capacity to produce reactive oxygen species, while RA supplementation had the opposite effect. These results are in line with the well-known function of retinoids in maintaining the homeostasis of the gut but support the idea that they have a proinflammatory effect by acting, in part, on the PMN population.
机译:肠出血性大肠杆菌(EHEC)是食源性病原体,会产生志贺毒素(Stx),并引起出血性结肠炎。在某些情况下,肠道内产生的Stx进入血流,导致全身并发症,可能导致致命的溶血尿毒症综合征。尽管像维生素A(VA)和视黄酸(RA)这样的类维生素A有益于肠道完整性和免疫系统,但补充VA对不同病因的胃肠道感染的作用一直存在争议。因此,这项工作的目的是研究不同VA状态对小鼠EHEC肠道感染结局的影响。我们报告说,VA缺乏症会在EHEC感染期间加重肠道损害,但同时会提高生存率。由于死亡主要与Stx毒性有关,因此静脉注射Stx来分析类维生素A水平是否会影响Stx敏感性。有趣的是,虽然VA缺乏症(VA-D)小鼠对Stx2的致死剂量具有抵抗力,但补充RA的小鼠对它的敏感性更高。鉴于已知外周血多形核细胞(PMN)增强Stx2毒性,我们研究了类维生素A水平对PMN绝对数量和功能的影响。我们发现VA-D小鼠的PMN数量减少,产生活性氧的能力降低,而RA的补充却相反。这些结果与类维生素A在维持肠道稳态方面的众所周知的功能相符,但支持这样的观点,即它们通过部分作用于PMN人群而具有促炎作用。

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