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 mice 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 homolog had no effect on bacterial colonization, gastritis, or neutrophilic inflammation. In contrast, these mutations had variable effects on IL-8 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 SS1, which did not induce IL-8 secretion, deletion of the cagII region or interruption of any 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.
Eaton
K A
KA
Department of Veterinary Biosciences, Ohio State University, Columbus, Ohio 43210, USA. eaton.1@osu.edu
Kersulyte
D
D
Mefford
M
M
Danon
S J
SJ
Krakowka
S
S
Berg
D E
DE
D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology*; D005756:Gastritis / Q000382:microbiology*; D005798:Genes, Bacterial; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D013552:Swine
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016209:Interleukin-8; C080866:cagA protein, Helicobacter pylori