title: Helicobacter pylori infection in mice: Role of outer membrane proteins in colonization and inflammation.
abstract: OBJECTIVE
  Mouse models of Helicobacter pylori infection have yielded variable results with respect to colonization and inflammation. We examined whether outer membrane proteins (OMPs) or the cag pathogenicity island (PAI) was responsible for some of this variability.
  
  
  METHODS
  C57BL/6 mice received clinical H. pylori isolates with different genotypes for the cag PAI and OMP gene switch status, as well as isogenic gene knockout mutants for cagE, oipA, babA2, hopZ, cagE/oipA, or oipA/hopZ. Bacterial density, histology, and mucosal cytokine/chemokine levels were measured after 4 and 12 weeks.
  
  
  RESULTS
  oipA, hopZ, hopO, and hopP switch status influenced both H. pylori density and colonization ability in mice. When 2 or more of the genes were "off," colonization rates were markedly reduced compared with those for strains with all genes "on" (from 58% to 0% after 12 weeks). oipA knockout mutants caused reduced inflammation and decreased mucosal interleukin 6 messenger RNA and KC messenger RNA and protein levels. H. pylori density and colonization ability were reduced if hopO or hopP switch status was changed from "on" to "off." There was a close relationship (r > 0.7) between the H. pylori density of the gastric mucosa of humans and mice when using the same H. pylori strains.
  
  
  CONCLUSIONS
  Many of the differences reported with mouse models may reflect subtle unrecognized differences (e.g., switch status of an OMP gene), emphasizing the necessity of characterizing isolates before and after experiments. The mouse model may be suitable for investigating factors related to colonization ability, H. pylori density, and gastric mucosal inflammation.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA. yyamaoka@bcm.tmc.edu
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kita
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kodama
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Imamura
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohno
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishimaru
authors.forename: Jiro
authors.initials: J
authors.lastname: Imanishi
authors.forename: David Y
authors.initials: DY
authors.lastname: Graham
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000502:physiology*; D054360:Chemokine CXCL1; D018925:Chemokines / Q000235:genetics; D019743:Chemokines, CXC; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000382:microbiology* / Q000503:physiopathology*; D016678:Genome; D005838:Genotype; D016481:Helicobacter Infections / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000235:genetics / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D013234:Stem Cells / Q000502:physiology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; C074302:keratinocyte-derived chemokines