Helicobacter pylori infection in mice:: Role of outer membrane proteins in colonization and inflammation

Background & Aims: Mouse models of Helicobacter pylori infection have yielded variable results with respect to colonization and inflammation. We examined whether outer membrane proteins (OMPs) or the cag pathogenicity island (PAI) was responsible for some of this variability. Methods: C57BL/6 mice received clinical H. pylori isolates with different genotypes for the cag PAI and OMP gene switch status, as well as isogenic gene knockout mutants for cagE, oipA, babA2, hopZ, cagE/oipA, or oipA/hopZ. Bacterial density, histology, and mucosal cytokine/chemokine levels were measured after 4 and 12 weeks. Results: oipA, hopZ, hopO, and hopP switch status influenced both H. pylori density and colonization ability in mice. When 2 or more of the genes were off, colonization rates were markedly reduced compared with those for strains with all genes on (from 58% to 0% after 12 weeks). oipA knockout mutants caused reduced inflammation and decreased mucosal interleukin 6 messenger RNA and KC messenger RNA and protein levels. H. pylori density and colonization ability were reduced if hopO or hopP switch status was changed from on to off. There was a close relationship (r > 0.7) between the H. pylori density of the gastric mucosa of humans and mice when using the same H. pylori strains. Conclusions: Many of the differences reported with mouse models may reflect subtle unrecognized differences (e.g., switch status of an OMP gene), emphasizing the necessity of characterizing isolates before and after experiments. The mouse model may be suitable for investigating factors related to colonization ability, H. pylori density, and gastric mucosal inflammation.