title: The Helicobacter pylori blood group antigen-binding adhesin facilitates bacterial colonization and augments a nonspecific immune response.
abstract: Presence of the Helicobacter pylori adherence factor blood group Ag-binding adhesin (BabA; binding to Lewis(b) (Le(b))) is associated with ulcer disease, adenocarcinoma, and precancerous lesions. The importance of BabA for bacterial colonization and the inflammatory response is unknown. A total of 141 antral biopsies from H. pylori-infected patients were assessed in regard to the degree of granulocytic (G0 degrees--G3 degrees) and lymphocytic (L1 degrees--L3 degrees) infiltration. DNA genotypes of babA2 (the transcriptionally active gene of BabA), cagA, and vacAs1/2 were determined by PCR. Colonization density and Le(b) status on gastric epithelial cells were determined by immunohistochemistry. Real-time quantitative (TaqMan) RT-PCR determined mRNA expression of IL-8, TNF -alpha, and the Th1 markers IFN-gamma and the IL-12R beta2 chain. A total of 91% of infected patients were Le(b) positive. The vacAs1(+)/cagA(+) strains harboring babA2 showed significantly higher levels of granulocytic infiltration, bacterial colonization, and IL-8 mRNA than vacAs1(+)/cagA(+) strains lacking babA2. IL-8 mRNA and protein production by KATO III cells in vitro increased dose dependently with addition of different numbers of type 1 strains (G27 and 2808 strains, 0.1--20 bacteria/cell). The mRNA expression of TNF-alpha, IFN-gamma, and IL-12R beta2 was higher in H. pylori-positive patients than in controls, but it did not differ significantly between patients infected with different strain types. These data suggest that BabA facilitates colonization of H. pylori and thereby increases IL-8 response, resulting in enhanced mucosal inflammation. Infection with strains harboring BabA thereby augment a nonspecific immune response, whereas the Th1 response toward H. pylori appears to be independent of BabA, cytotoxin-associated gene A, or vacuolating cytotoxin.
authors.affiliation: Departments of Medicine II and Gastroenterology, Microbiology, and Pathology, Technical University of Munich, Munich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Rad
authors.forename: Markus
authors.initials: M
authors.lastname: Gerhard
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Martin
authors.initials: M
authors.lastname: Schöniger
authors.forename: Thomas
authors.initials: T
authors.lastname: Rösch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schepp
authors.forename: Ingrid
authors.initials: I
authors.lastname: Becker
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Christian
authors.initials: C
authors.lastname: Prinz
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology*; D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D015169:Colony Count, Microbial; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D005798:Genes, Bacterial; D005838:Genotype; D006098:Granulocytes / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D007983:Lewis Blood Group Antigens / Q000737:chemistry / Q000276:immunology; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology; D011706:Pyloric Antrum / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000382:microbiology
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; C400429:BabA protein, Helicobacter pylori; D002352:Carrier Proteins; D016209:Interleukin-8; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; C404741:galactopyranosyl-1-3-galactopyranosyl-1-3(4)-N-acetylglucosamine