Mohammadi M, Redline R, Nedrud J, Czinn S
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Infect Immun. 1996 Jan;64(1):238-45. doi: 10.1128/iai.64.1.238-245.1996.
In humans, Helicobacter pylori establishes a chronic infection which can result in various degrees of gastric inflammation, peptic ulcer disease, and a predisposition to gastric cancer. It has been suggested that bacterial virulence factors such as the vacuolating toxin (VacA) and the cytotoxin-associated gene product (CagA) may play a major role in determining the clinical outcome of Helicobacter infections. The role of host responses in these varied outcomes has received little attention. Helicobacter felis, which does not express CagA or VacA, causes chronic infection and inflammation in a well-characterized mouse model. We have used this model to evaluate the role of host responses in Helicobacter infections. BALB/c, C3H, and C57BL/6 mice were orally infected with a single strain of H. felis, and 2 and 11 weeks after infection, the mice were sacrificed and evaluated histologically for magnitude of H. felis infection. Intensity and extent of inflammation, and cellular composition of the inflammatory infiltrate. All three strains of mice demonstrated comparable levels of infection at 11 weeks, but the pattern and intensity of inflammation varied from minimal in BALB/c mice to severe in C57BL/6 mice. Gastric epithelial erosions were noted in C3H mice, and mucous cell hyperplasia was observed in C3H and C57BL/6 mice. Abundant mucosal mast cells were observed in the gastric tissues of all three mouse strains. Studies using major histocompatibility complex (MHC)-congenic mice revealed probable contributions by both MHC and non-MHC genes to Helicobacter-induced inflammation. Thus, large variations in the severity of disease were observed after infection of different inbred strains and congenic mice with a single isolate of H. felis. These results demonstrate the importance of the host response in disease outcome following gastric Helicobacter infection.
在人类中，幽门螺杆菌会引发慢性感染，可导致不同程度的胃部炎症、消化性溃疡疾病以及患胃癌的倾向。有人提出，诸如空泡毒素（VacA）和细胞毒素相关基因产物（CagA）等细菌毒力因子可能在决定幽门螺杆菌感染的临床结果中起主要作用。宿主反应在这些不同结果中的作用却很少受到关注。猫幽门螺杆菌不表达CagA或VacA，在一个特征明确的小鼠模型中会引发慢性感染和炎症。我们利用这个模型来评估宿主反应在幽门螺杆菌感染中的作用。将BALB/c、C3H和C57BL/6小鼠口服感染单一菌株的猫幽门螺杆菌，感染后2周和11周，处死小鼠并进行组织学评估，以确定猫幽门螺杆菌感染的程度、炎症的强度和范围以及炎性浸润的细胞组成。所有三种品系的小鼠在11周时感染水平相当，但炎症的模式和强度各不相同，从BALB/c小鼠中的轻微炎症到C57BL/6小鼠中的严重炎症。在C3H小鼠中发现胃上皮糜烂，在C3H和C57BL/6小鼠中观察到黏液细胞增生。在所有三种品系小鼠的胃组织中均观察到大量黏膜肥大细胞。使用主要组织相容性复合体（MHC）同基因小鼠的研究表明，MHC基因和非MHC基因可能都对幽门螺杆菌诱导的炎症有影响。因此，用单一分离株的猫幽门螺杆菌感染不同近交系和同基因小鼠后，观察到疾病严重程度有很大差异。这些结果证明了宿主反应在胃部幽门螺杆菌感染后疾病转归中的重要性。
