Role ofHelicobacter pylori cagRegion Genes in Colonization and Gastritis in Two Animal Models

Abstract

TheHelicobacter pylorichromosomal region known as the cytotoxin-gene associated pathogenicity island (cagPAI) 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 thecagPAI, induction of IL-8, and induction of neutrophilic gastric inflammation. Germ-free neonatal piglets and conventional C57BL/6 mice were given wild-type orcagdeficient mutant derivatives ofH. pyloristrain 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 entirecagregion or interruption of thevirB10orvirB11homolog had no effect on bacterial colonization, gastritis, or neutrophilic inflammation. In contrast, these mutations had variable effects on IL-8 induction, depending on theH. pyloristrain. In the piglet-adapated strain 26695, which induced IL-8 secretion by AGS cells, deletion of thecagPAI decreased induction. In the mouse-adapted strain SS1, which did not induce IL-8 secretion, deletion of thecagII region or interruption of any of threecagregion genes increased IL-8 induction. These results indicate that in mice and piglets (i) neither thecagPAI 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 thecagPAI, IL-8 induction, and neutrophilic gastritis.