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Involvement of T helper type 17 and regulatory T cell activity in Citrobacter rodentium invasion and inflammatory damage

机译:T型辅助细胞17型和调节性T细胞活性参与啮齿动物柠檬酸杆菌的侵袭和炎性损害

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摘要

Citrobacter rodentium is a murine pathogen that transiently colonizes the lumen of the large intestine. C. rodentium induces colitis, but the relative importance and temporal induction of the T helper type 17 (Th17) and regulatory T cell (Treg) pathways in protection from the infection and inflammation have not been assessed. Our aim was to investigate the key immunological signalling events associated with successful clearance of C. rodentium. Mice were challenged with luminescent-tagged C. rodentium and killed at days 3 (early infection), 10 (peak infection) and 21 (late infection) post-infection. Bioluminescent imaging and bacterial culture determined levels of C. rodentium. Distal colon mRNA expression of interleukin (IL)-17, IL-6, IL-1β, tumour necrosis factor (TNF)-α, forkhead box P3 (FoxP3) and ghrelin were assessed using real-time polymerase chain reaction. Results were compared with age-matched non-infected mice. Low levels of C. rodentium were found at day 3, high levels at day 10, with clearance from the majority of the mice by day 21. In the distal colon, there was up-regulation of TNF-α and FoxP3 throughout the study and increases in IL-6 and IL-17 during the peak and late stages of infection. Ghrelin expression was increased at the peak and late stages of infection. This study has characterized changes to the T helper cell pathways, following the course of C. rodentium infection in mice. There were significant immunological changes, with up-regulation of the Th17 and Treg pathways in the distal colon and an increase in ghrelin expression compared with non-infected control mice. These changes may play a role in the pathology and clearance of C. rodentium.
机译:啮齿类柠檬酸杆菌是一种鼠类病原体,可暂时定居在大肠腔中。啮齿类动物可诱发结肠炎,但尚未评估T辅助型17(Th17)和调节性T细胞(Treg)途径在预防感染和炎症方面的相对重要性和暂时诱导作用。我们的目的是研究与成功清除啮齿类念珠菌有关的关键免疫信号事件。在小鼠感染后第3天(早期感染),第10天(峰值感染)和第21天(晚期感染)用发光标记的啮齿类啮齿动物攻击小鼠并杀死。生物发光成像和细菌培养确定了啮齿类动物的水平。使用实时聚合酶链反应评估白细胞介素(IL)-17,IL-6,IL-1β,肿瘤坏死因子(TNF)-α,叉头盒P3(FoxP3)和生长素释放肽的远端结肠mRNA表达。将结果与年龄匹配的未感染小鼠进行比较。在第3天发现低水平的啮齿类啮齿动物,在第10天发现高水平的啮齿类动物,到第21天已从大多数小鼠中清除。在整个研究过程中,远端结肠中的TNF-α和FoxP3上调,并且在感染的高峰期和后期,IL-6和IL-17升高。在感染的高峰和晚期,Ghrelin表达增加。这项研究的特征是在小鼠中感染了啮齿类念珠菌后,T辅助细胞途径发生了变化。与未感染的对照小鼠相比,存在显着的免疫学变化,远端结肠中的Th17和Treg通路上调,且生长素释放肽表达增加。这些变化可能在啮齿类念珠菌的病理学和清除中起作用。

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