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首页> 外文期刊>Infection and immunity >Citrobacter rodentium Infection in Mice Elicits a Mucosal Th1 Cytokine Response and Lesions Similar to Those in Murine Inflammatory Bowel Disease
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Citrobacter rodentium Infection in Mice Elicits a Mucosal Th1 Cytokine Response and Lesions Similar to Those in Murine Inflammatory Bowel Disease

机译：小鼠柠檬酸杆菌感染引起粘膜Th1细胞因子反应和病变类似于小鼠炎症性肠病。

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Citrobacter rodentium is a classically noninvasive pathogen of mice that is similar to enteropathogenic Escherichia coli (EPEC) in man. Following oral infection of young mice, the organism colonizes the distal colon, and within 1 week the colonic mucosa doubles in thickness and there is massive epithelial cell hyperplasia. Since T-cell responses in mouse models of inflammatory bowel disease (IBD) also cause epithelial hyperplasia, we have investigated the possibility that C. rodentium promotes similar T-cell responses in the mucosa, thereby increasing epithelial shedding, transmission, and replication of the organism. Beginning 6 days after infection, bacteria were observed to be in close association with the epithelial surface and were also visible scattered throughout the lamina propria and in the submucosa. There was a CD3+-cell infiltrate into the colonic lamina propria and epithelium as well as mucosal thickening and crypt hyperplasia. The majority of CD3+ cells were CD4+ and were not γδ+. Reverse transcription-PCR analysis of cytokines also revealed a highly polarized Th1 response (interleukin-12, gamma interferon, and tumor necrosis factor alpha) in the mucosa and a large increase in the epithelial cell mitogen keratinocyte growth factor. None of the changes were seen in mice inoculated with bacteria lacking intimin (which is necessary for colonization), but they were seen in mice inoculated with C. rodentium complemented with intimin from EPEC. This is the first example of a classically noninvasive bacterial pathogen which elicits a strong mucosal Th1 response and which produces pathology similar to that seen in mouse models of IBD, which is also characterized by a strong Th1 response. These results also suggest that the colonic mucosa responds in a stereotypic way to Th1 responses.
机译：啮齿类柠檬酸杆菌是一种经典的小鼠非侵入性病原体，与人的肠道致病性大肠杆菌（EPEC）相似。幼鼠经口感染后，该生物体定居在远端结肠，并且在1周内结肠粘膜的厚度增加了一倍，并且出现大量的上皮细胞增生。由于炎症性肠病（IBD）小鼠模型中的T细胞反应也引起上皮增生，因此我们研究了 C的可能性。啮齿动物在粘膜中促进相似的T细胞反应，从而增加了生物体的上皮脱落，传播和复制。感染后6天开始，观察到细菌与上皮表面紧密相关，并且还可见散布在整个固有层和粘膜下层。 CD3 + 细胞浸润到结肠固有层和上皮细胞中，以及粘膜增厚和隐窝增生。大多数CD3 + 细胞是CD4 + ，而不是γδ + 。细胞因子的逆转录-PCR分析还显示粘膜中高度极化的Th1反应（白介素12，γ干扰素和肿瘤坏死因子α）和上皮细胞有丝分裂原角质形成细胞生长因子的大量增加。在接种缺乏intimin细菌的细菌的小鼠（定植是必需的）中，没有观察到任何变化，但是在接种了 C的小鼠中，没有观察到这些变化。啮齿类动物辅以EPEC的intimin。这是经典的非侵入性细菌病原体的第一个例子，它引起强烈的粘膜Th1反应，并产生类似于在IBD小鼠模型中观察到的病理，其特征还在于强烈的Th1反应。这些结果还表明，结肠粘膜以定型的方式对Th1反应作出反应。

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