Role of Helicobacter pylori cag region genes in colonization and gastritis in two animal models

The Helicobacter pylori chromosomal region known as the cytotoxin-gene associated pathogenicity island (cag PAI) is associated with severe disease and encodes proteins that are believed to induce interleukin (IL-8) secretion by cultured epithelial cells. The objective of this study was to evaluate the relationship between the cag PAI, induction of IL-8, and induction of neutrophilic gastric inflammation. Germ-free neonatal piglets and conventional C57BL/6 mite were given wild-type or cag deficient mutant derivatives of H, pylori strain 26695 or SS1. Bacterial colonization was determined by plate count, gastritis and neutrophilic inflammation were quantified, and IL-8 induction in AGS cells was determined by enzyme-linked immunosorbent assay. Deletion of the entire cag region or interruption of the virB10 or virB11 hom;log had no effect on bacterial colonization, gastritis, or neutrophilic inflammation. In contrast, these mutations had variable effects on IL S induction, depending on the H, pylori strain. In the piglet-adapated strain 26695, which induced IL-8 secretion by, AGS cells, deletion of the cag PAI decreased induction. In the mouse adapted strain SSI, which did not induce IL-8 secretion, deletion of the cagII region or interruption of an!: of three cag region genes increased IL-8 induction. These results indicate that in mice and piglets (i) neither the cag PAI nor the ability to induce IL-8 in vitro is essential for colonization or neutrophilic inflammation and (ii) there is no direct relationship between the presence of the cag PAI, IL-8 induction, and neutrophilic gastritis.