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

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...

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Bibliographic Details
Published in:PloS one 2009-03, Vol.4 (3), p.e4754-e4754
Main Authors: Wiedemann, Tobias, Loell, Eva, Mueller, Susanna, Stoeckelhuber, Mechthild, Stolte, Manfred, Haas, Rainer, Rieder, Gabriele
Format: Article
Language:English
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
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0004754