Abstract
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.