ROLE OF THE HOST IN PATHOGENESIS OF HELICOBACTER-ASSOCIATED GASTRITIS- H-FELIS INFECTION OF INBRED AND CONGENIC MOUSE STRAINS

In humans, Helicobacter pylori establishes a chronic infection which c an result in various degrees of gastric inflammation, peptic ulcer dis ease, and a predisposition to gastric cancer, it has been suggested th at bacterial virulence factors such as the vacuolating toxin (VacA) an d the cytotoxin-associated gene product (CagA) may play a major role i n determining the clinical outcome of Helicobacter infections, The rol e of host responses in these varied outcomes has received little atten tion Helicobacter felis, which does not express CagA or VacA, causes c hronic infection and inflammation in a well-characterized mouse model. We have used this model to evaluate the role of host responses in Hel icobacter infections, BALB/c, C3H, and C57BL/6 mice were orally infect ed with a single strain of H, felis, and 2 and 11 weeks after infectio n, the mice were sacrificed and evaluated histologically for magnitude of H. felis infection, intensity and extent of inflammation. and cell ular 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 mi ce to severe in C57BL/6 mice. Gastric epithelial erosions were noted i n C3H mice, and mucous cell hyperplasia was observed in C3H and C57BL/ 6 mice. Abundant mucosal mast cells were observed in the gastric tissu es of all three mouse strains, Studies using major histocompatibility complex (MHC)-congenic mice revealed probable contributions by both MH C acid non-MHC gems 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.