title: Role of γ-glutamyltranspeptidase in the pathogenesis of Helicobacter suis and Helicobacter pylori infections.
abstract: Helicobacter (H.) suis can colonize the stomach of pigs as well as humans, causing chronic gastritis and other gastric pathological changes including gastric ulceration and mucosa-associated lymphoid tissue (MALT) lymphoma. Recently, a virulence factor of H. suis, γ-glutamyl transpeptidase (GGT), has been demonstrated to play an important role in the induction of human gastric epithelial cell death and modulation of lymphocyte proliferation depending on glutamine and glutathione catabolism. In the present study, the relevance of GGT in the pathogenesis of H. suis infection was studied in mouse and Mongolian gerbil models. In addition, the relative importance of H. suis GGT was compared with that of the H. pylori GGT. A significant and different contribution of the GGT of H. suis and H. pylori was seen in terms of bacterial colonization, inflammation and the evoked immune response. In contrast to H. pyloriΔggt strains, H. suisΔggt strains were capable of colonizing the stomach at levels comparable to WT strains, although they induced significantly less overall gastric inflammation in mice. This was characterized by lower numbers of T and B cells, and a lower level of epithelial cell proliferation. In general, compared to WT strain infection, ggt mutant strains of H. suis triggered lower levels of Th1 and Th17 signature cytokine expression. A pronounced upregulation of B-lymphocyte chemoattractant CXCL13 was observed, both in animals infected with WT and ggt mutant strains of H. suis. Interestingly, H. suis GGT was shown to affect the glutamine metabolism of gastric epithelium through downregulation of the glutamine transporter ASCT2.
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, 9820, Merelbeke, Belgium. guangzhi.zhang@ugent.be.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, 9820, Merelbeke, Belgium. richard.ducatelle@ugent.be.
authors.forename: Richard
authors.initials: R
authors.lastname: Ducatelle
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, 9820, Merelbeke, Belgium. eadbruyn.debruyne@ugent.be.
authors.forename: Ellen
authors.initials: E
authors.lastname: De Bruyne
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, 9820, Merelbeke, Belgium. myrthe.joosten@ugent.be.
authors.forename: Myrthe
authors.initials: M
authors.lastname: Joosten
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, 9820, Merelbeke, Belgium. iris.bosschem@UGent.be.
authors.forename: Iris
authors.initials: I
authors.lastname: Bosschem
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, 9820, Merelbeke, Belgium. annemieke.smet@ugent.be.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Smet
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, 9820, Merelbeke, Belgium. freddy.haesebrouck@ugent.be.
authors.forename: Freddy
authors.initials: F
authors.lastname: Haesebrouck
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, 9820, Merelbeke, Belgium. bram.flahou@ugent.be.
authors.forename: Bram
authors.initials: B
authors.lastname: Flahou
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology / Q000662:veterinary*; D018247:Helicobacter heilmannii / Q000502:physiology*; D016480:Helicobacter pylori / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013552:Swine; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; D005723:gamma-Glutamyltransferase