Whary M T, Danon S J, Feng Y, Ge Z, Sundina N, Ng V, Taylor N S, Rogers A B, Fox J G
Division of Comparative Medicine, Massachusette Institute of Technology, 77 Massachusetts Avenue, Bldg. 16-825A, Cambridge, MA 02139, USA.
Infect Immun. 2006 Dec;74(12):6615-23. doi: 10.1128/IAI.01091-06. Epub 2006 Sep 18.
Infection with Helicobacter trogontum, a urease-positive helicobacter isolated from subclinically infected rats, was evaluated in B6.129P2-IL10(tm1Cgn) (interleukin-10(-/-) [IL-10(-/-)]) and C57BL/6 (B6) mice. In a first experiment, IL-10(-/-) mice naturally infected with Helicobacter rodentium had subclinical typhlocolitis but developed severe diarrhea and loss of body condition with erosive to ulcerative typhlocolitis within 1 to 3 weeks of experimental infection with H. trogontum. A second experiment demonstrated that helicobacter-free IL-10(-/-) mice dosed with H. trogontum also developed severe clinical signs and typhlocolitis within 2 to 4 weeks, whereas B6 mice colonized with H. trogontum were resistant to disease. In a third experiment, using helicobacter-free IL-10(-/-) mice, dosing with H. trogontum resulted in acute morbidity and typhlocolitis within 8 days. Acute typhlocolitis was accompanied by signs of sepsis supported by degenerative hemograms and recovery of Escherichia coli and Proteus spp. from the livers of infected mice. Quantitative PCR data revealed that H. rodentium and H. trogontum may compete for colonization of the lower bowel, as H. trogontum established higher colonization levels in the absence of H. rodentium (P < 0.003). H. trogontum-induced typhlocolitis was also associated with a significant decrease in the levels of colonization by five of eight anaerobes that comprise altered Schaedler's flora (P < 0.002). These results demonstrate for the first time that H. rodentium infection in IL-10(-/-) mice causes subclinical typhlocolitis and that infection with H. trogontum (with or without H. rodentium) induces a rapid-onset, erosive to ulcerative typhlocolitis which impacts the normal anaerobic flora of the colon and increases the risk of sepsis.
从亚临床感染大鼠中分离出的脲酶阳性幽门螺杆菌——trogontum幽门螺杆菌(Helicobacter trogontum)感染,在B6.129P2-IL10(tm1Cgn)(白细胞介素-10基因敲除[IL-10(-/-)])小鼠和C57BL/6(B6)小鼠中进行了评估。在第一个实验中,自然感染啮齿类幽门螺杆菌(Helicobacter rodentium)的IL-10(-/-)小鼠患有亚临床盲结肠炎,但在感染trogontum幽门螺杆菌的实验感染后1至3周内出现严重腹泻和身体状况下降,并伴有糜烂性至溃疡性盲结肠炎。第二个实验表明,给无幽门螺杆菌的IL-10(-/-)小鼠接种trogontum幽门螺杆菌后,在2至4周内也出现了严重的临床症状和盲结肠炎,而接种trogontum幽门螺杆菌的B6小鼠对疾病具有抵抗力。在第三个实验中,使用无幽门螺杆菌的IL-10(-/-)小鼠,接种trogontum幽门螺杆菌后8天内出现急性发病和盲结肠炎。急性盲结肠炎伴有败血症迹象,表现为血液学指标退化以及从感染小鼠肝脏中分离出大肠杆菌和变形杆菌属。定量PCR数据显示,啮齿类幽门螺杆菌和trogontum幽门螺杆菌可能竞争下消化道的定植,因为在没有啮齿类幽门螺杆菌的情况下,trogontum幽门螺杆菌建立了更高的定植水平(P < 0.003)。trogontum幽门螺杆菌诱导的盲结肠炎还与构成改变的舍德勒菌群的八种厌氧菌中的五种的定植水平显著降低有关(P < 0.002)。这些结果首次证明,IL-10(-/-)小鼠中的啮齿类幽门螺杆菌感染会导致亚临床盲结肠炎,并且trogontum幽门螺杆菌感染(无论是否伴有啮齿类幽门螺杆菌)会诱发快速发作的、糜烂性至溃疡性盲结肠炎,这会影响结肠的正常厌氧菌群并增加败血症风险。