Development of fatal colitis in FVB mice infected with Citrobacter rodentium
Development of fatal colitis in FVB mice infected with Citrobacter rodentium
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DOI：
10.1128/iai.01810-06
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发表时间：
2007-07-01
影响因子：
3.1
通讯作者：
Schauer, David B.
中科院分区：
文献类型：
--
作者：
Borenshtein, Diana;Nambiar, Prashant R.;Schauer, David B.
鼠柠檬酸杆菌是传染性小鼠结肠增生的病原体。该疾病的特征是在多种遗传背景的成年小鼠降结肠中出现严重但暂时的上皮增生，炎症有限。这种小鼠病原体感染的自然史已在远交系瑞士 Webster（SW）小鼠中得到描述，但在同源近交系FVB品系中尚未明确。与SW小鼠的亚临床感染不同，12周龄的FVB小鼠在接种后9天（dpi）开始出现明显疾病，体重显著减轻且有死亡情况。到21 dpi时，超过75%的感染FVB小鼠死亡或不得不被安乐死，而SW小鼠无死亡情况。通过补液疗法可完全防止FVB小鼠死亡。在9 dpi之前，两组小鼠的细菌粪便排菌情况相似；然而，在12至18 dpi时，观察到FVB小鼠的细菌清除有轻微但显著的延迟。SW小鼠在降结肠中出现增生，炎症极轻微。FVB小鼠在接种后6 dpi时，降结肠出现上皮细胞过度增殖、伴有糜烂和溃疡的严重炎症以及上皮异型性。在大多数存活的FVB小鼠中，结肠病变（包括上皮异型性）是可逆的，尽管有一小部分（5% - 7%）在接种后7个月仍表现出慢性结肠炎。具有相似遗传背景的易感和抗性小鼠品系的存在将有助于识别导致感染结果的宿主因素，并可能促使开发预防和治疗感染性结肠炎的新策略。
Citrobacter rodentium is the causative agent of transmissible murine colonic hyperplasia. The disease is characterized by severe but temporary epithelial hyperplasia with limited inflammation in the descending colon of adult mice on a variety of genetic backgrounds. The natural history of infection with this murine pathogen has been characterized in outbred Swiss Webster (SW) mice but not in the cognate inbred FVB strain. In contrast to subclinical infection in SW mice, 12-week-old FVB mice developed overt disease with significant weight loss and mortality beginning by 9 days postinoculation (dpi). By 21 dpi, more than 75% of infected FVB mice died or had to be euthanized, whereas no mortality developed in SW mice. Mortality in FVB mice was fully prevented by fluid therapy. Fecal shedding of bacteria was similar in both groups through 9 dpi; however, a slight but significant delay in bacterial clearance was observed in FVB mice by 12 to 18 dpi. SW mice developed hyperplasia with minimal inflammation in the descending colon. FVB mice developed epithelial cell hyperproliferation, severe inflammation with erosions and ulcers, and epithelial atypia by 6 dpi in the descending colon. In the majority of surviving FVB mice, colonic lesions, including epithelial atypia, were reversible, although a small percentage (5 to 7%) exhibited chronic colitis through 7 months postinoculation. The existence of susceptible and resistant lines of mice with similar genetic backgrounds will facilitate the identification of host factors responsible for the outcome of infection and may lead to the development of novel strategies for preventing and treating infectious colitis.