Borenshtein Diana, Nambiar Prashant R, Groff Elizabeth B, Fox James G, Schauer David B
Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Infect Immun. 2007 Jul;75(7):3271-81. doi: 10.1128/IAI.01810-06. Epub 2007 Apr 30.
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.
鼠柠檬酸杆菌是传染性小鼠结肠增生的病原体。该疾病的特征是在各种遗传背景的成年小鼠降结肠中出现严重但短暂的上皮增生，炎症有限。这种鼠类病原体感染的自然史已在远交系瑞士韦伯斯特（SW）小鼠中得到描述，但在同源近交系FVB品系中尚未描述。与SW小鼠的亚临床感染不同，12周龄的FVB小鼠在接种后9天开始出现明显疾病，体重显著减轻并出现死亡。到接种后21天，超过75%的受感染FVB小鼠死亡或不得不实施安乐死，而SW小鼠未出现死亡。通过液体疗法可完全预防FVB小鼠的死亡。在接种后9天内，两组小鼠的粪便细菌排出情况相似；然而，在接种后12至18天观察到FVB小鼠的细菌清除略有但显著延迟。SW小鼠降结肠出现增生，炎症轻微。FVB小鼠在接种后6天，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增生。在大多数存活的FVB小鼠中，结肠病变，包括上皮异型增生，是可逆的，尽管有一小部分（5%至7%）在接种后7个月表现为慢性结肠炎。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确定负责感染结果的宿主因素，并可能导致开发预防和治疗感染性结肠炎的新策略。
