Helicobacter pylori cag-Pathogenicity island-dependent early immunological response triggers later precancerous gastric changes in Mongolian gerbils

• Published in: PloS one Vol. 4; no. 3; p. e4754
• Main Authors: Wiedemann, Tobias, Loell, Eva, Mueller, Susanna, Stoeckelhuber, Mechthild, Stolte, Manfred, Haas, Rainer, Rieder, Gabriele
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.03.2009; Public Library of Science (PLoS)
• Subjects: Achlorhydria - immunology; Achlorhydria - microbiology; Achlorhydria - pathology; Animals; Antigens, Bacterial - genetics; Antiulcer agents; Apoptosis; Atrophy; Bacterial Proteins - genetics; Bioindicators; Colonization; Cytokines; Cytokines - genetics; Cytokines - metabolism; Dysplasia; Gastric cancer; Gastrins; Gastritis; Gastritis - immunology; Gastritis - microbiology; Gastritis - pathology; Gastroenterology and Hepatology; Gastroenterology and Hepatology/Gastrointestinal Cancers; Gastroenterology and Hepatology/Gastrointestinal Infections; Gastroenterology and Hepatology/Stomach and Duodenum; Gastrointestinal diseases; Genomic Islands; Genotype & phenotype; Gerbillinae - genetics; Health aspects; Health risks; Helicobacter Infections - complications; Helicobacter Infections - genetics; Helicobacter Infections - pathology; Helicobacter pylori; Helicobacter pylori - genetics; Helicobacter pylori - pathogenicity; Hygiene; Hypertrophy; Immune response; Immunoenzyme Techniques; Immunohistochemistry; Immunology; Immunology/Immunity to Infections; Infection; Infections; Infectious Diseases/Bacterial Infections; Infectious Diseases/Gastrointestinal Infections; Inflammation; Medical research; Metaplasia; Microbiology/Cellular Microbiology and Pathogenesis; Microbiology/Medical Microbiology; Mucosa; Oncology/Gastrointestinal Cancers; Paraffin; Parietal cells; Pathogenicity; Pathogens; Pathology/Histopathology; Pathology/Pathophysiology; Physiological aspects; Physiology; Polyamide-imides; Polymerase chain reaction; Precancerous Conditions - immunology; Precancerous Conditions - microbiology; Precancerous Conditions - pathology; Radioimmunoassay; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Somatostatin; Stomach cancer; Stomach Neoplasms - immunology; Stomach Neoplasms - microbiology; Stomach Neoplasms - pathology; Stomach Ulcer - immunology; Stomach Ulcer - microbiology; Stomach Ulcer - pathology; Studies; Trinucleotide repeats; Ulcers; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004754

Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS) to inject the Cytotoxin associated antigen (CagA) into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI) for the induction of gastric ulcer and precancerous conditions over time (2-64 weeks) using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT), or an isogenic B128DeltacagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4-8 weeks) occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies.