Helicobacter pylori-associated gastritis in mice is host and strain specific.
The vacA and cagA geno- and phenotypes of two mouse-adapted strains of Helicobacter pylori, SS1 and SPM326, were determined. The SS1 strain, which had the cagA+ and vacA s2-m2 genotype, induced neither vacuole formation in HeLa cells nor interleukin-8 (IL-8) production in KATO III cells. In contrast, H. pylori SPM326, with the cagA+ and vacA s1b-m1 genotype, induced vacuoles as well as IL-8 production in vitro. Furthermore, a spontaneous mutant of SPM326, which produced a vacuolating cytotoxin but was not able to induce IL-8 production (SPM326/IL-8(-)), was detected. C57Bl/6 and BALB/c mice were infected with these three strains to investigate the colonization pattern and the effect on the immune response in vivo. The SS1 strain colonized the stomachs of all mice in large numbers which remained constant over time. Colonization with the SPM326/IL-8(+) and SPM326/IL-8(-) strains was lesser, or even absent, and decreased over time. At 5 weeks postinoculation all three H. pylori strains induced a mild increase of neutrophil count in the gastric corpus of C57Bl/6 mice, which disappeared by 12 weeks. At both 5 and 12 weeks postinoculation C57Bl/6 mice colonized with SPM326/IL-8(+) showed an increased expression of major histocompatibility complex (MHC) class II antigen in the cardia which was accompanied by an increased number of T cells. C57Bl/6 mice that were infected with SS1 and SPM326/IL-8(-) did not show chronic inflammation. BALB/c mice colonized with SS1 and SPM326/IL-8(-) also showed an increase in neutrophil count at 5 weeks, which normalized again by 12 weeks postinoculation. At this time point SS1-infected mice showed inflammation in the corpus and antrum. At these sites an increased expression of MHC class II antigens and an increased number of T cells were observed. Although small lymphoid follicles were already observed 5 weeks after inoculation with SS1, their incidence as well as their number was increased at 12 weeks. These results show that inflammation induced by H. pylori depends both on the bacterial strain and the host.
van Doorn
N E
NE
Departments of Medical Microbiology, School of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Namavar
F
F
Sparrius
M
M
Stoof
J
J
van Rees
E P
EP
van Doorn
L J
LJ
Vandenbroucke-Grauls
C M
CM
D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D003603:Cytotoxins / Q000235:genetics / Q000276:immunology; D005260:Female; D005756:Gastritis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005838:Genotype; D006367:HeLa Cells; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013045:Species Specificity; D013270:Stomach / Q000382:microbiology; D014617:Vacuoles
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori