盲肠定殖对于假结核耶尔森菌持续性感染的发展很重要。

Colonization of cecum is important for development of persistent infection by Yersinia pseudotuberculosis.

作者信息

Fahlgren Anna, Avican Kemal, Westermark Linda, Nordfelth Roland, Fällman Maria

机构信息

Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden

Department of Molecular Biology, Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå, Sweden Laboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå, Sweden.

出版信息

Infect Immun. 2014 Aug;82(8):3471-82. doi: 10.1128/IAI.01793-14. Epub 2014 Jun 2.

Abstract

Yersiniosis is a human disease caused by the bacterium Yersinia pseudotuberculosis or Yersinia enterocolitica. The infection is usually resolved but can lead to postinfectious sequelae, including reactive arthritis and erythema nodosum. The commonly used Yersinia mouse infection model mimics acute infection in humans to some extent but leads to systemic infection and eventual death. Here, we analyzed sublethal infection doses of Y. pseudotuberculosis in mice in real time using bioluminescent imaging and found that infections using these lower doses result in extended periods of asymptomatic infections in a fraction of mice. In a search for the site for bacterial persistence, we found that the cecum was the primary colonization site and was the site where the organism resided during a 115-day infection period. Persistent infection was accompanied by sustained fecal shedding of cultivable bacteria. Cecal patches were identified as the primary site for cecal colonization during persistence. Y. pseudotuberculosis bacteria were present in inflammatory lesions, in localized foci, or as single cells and also in neutrophil exudates in the cecal lumen. The chronically colonized cecum may serve as a reservoir for dissemination of infection to extraintestinal sites, and a chronic inflammatory state may trigger the onset of postinfectious sequelae. This novel mouse model for bacterial persistence in cecum has potential as an investigative tool to unveil a deeper understanding of bacterial adaptation and host immune defense mechanisms during persistent infection.

摘要

耶尔森菌病是一种由假结核耶尔森菌或小肠结肠炎耶尔森菌引起的人类疾病。感染通常会自行痊愈,但可能导致感染后后遗症,包括反应性关节炎和结节性红斑。常用的耶尔森菌小鼠感染模型在一定程度上模拟了人类的急性感染,但会导致全身感染并最终死亡。在此,我们使用生物发光成像实时分析了小鼠体内假结核耶尔森菌的亚致死感染剂量,发现使用这些较低剂量进行感染会使一部分小鼠出现无症状感染的时间延长。在寻找细菌持续存在的部位时,我们发现盲肠是主要的定植部位,也是该生物体在115天感染期内驻留的部位。持续性感染伴随着可培养细菌的持续粪便排出。盲肠斑块被确定为持续性感染期间盲肠定植的主要部位。假结核耶尔森菌存在于炎性病变、局部病灶中,或呈单个细胞形式,也存在于盲肠腔内的中性粒细胞渗出物中。长期定植的盲肠可能作为感染传播到肠外部位的储存库,慢性炎症状态可能引发感染后后遗症的发作。这种用于细菌在盲肠中持续存在的新型小鼠模型有潜力作为一种研究工具,以更深入地了解持续性感染期间细菌的适应性和宿主免疫防御机制。

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