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Updated: Oct 21, 2026
Mouse Models Of Helicobacter Infection And Gastric Pathologies
Published on: October 18, 2018
Helicobacter pylori-associated gastritis in mice is host and strain specific
N E van Doorn1, F Namavar, M Sparrius
1Departments of Medical Microbiology, School of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Abstract:
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.
Insights
Helicobacter pylori strain type influences stomach inflammation and immune response in mice. Different bacterial genotypes, vacA and cagA, dictate vacuole formation, IL-8 production, and host immune cell activity, impacting chronic inflammation development.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Helicobacter pylori (H. pylori) infection is a major cause of gastritis and peptic ulcers.
- The virulence factors vacA and cagA play significant roles in H. pylori pathogenesis.
- Understanding strain-specific differences is crucial for predicting disease outcomes.
Purpose of the Study:
- To characterize the vacA and cagA genotypes and phenotypes of two mouse-adapted H. pylori strains (SS1 and SPM326).
- To investigate the in vivo colonization patterns and immune responses induced by these strains in different mouse models.
- To determine the correlation between bacterial virulence factors and the development of gastric inflammation.
Main Methods:
- Genotyping and phenotyping of H. pylori strains SS1 and SPM326 for vacA and cagA.
- In vitro assays for vacuole formation and IL-8 production.
- Infection of C57Bl/6 and BALB/c mice with H. pylori strains.
- Analysis of gastric colonization, neutrophil counts, MHC class II expression, and T cell infiltration at different time points.
Main Results:
- H. pylori SS1 (cagA+, vacA s2-m2) did not induce vacuole formation or IL-8 production, colonized mice effectively, and did not cause chronic inflammation.
- H. pylori SPM326 (cagA+, vacA s1b-m1) induced vacuole formation and IL-8 production, with variable colonization and transient neutrophil increase.
- SPM326/IL-8(-) mutant showed reduced colonization and no chronic inflammation, while SPM326/IL-8(+) induced MHC class II expression and T cell increase in C57Bl/6 mice.
- BALB/c mice infected with SS1 showed inflammation, increased MHC class II, T cells, and lymphoid follicles in the corpus and antrum by 12 weeks.
Conclusions:
- H. pylori-induced gastric inflammation is dependent on both the bacterial strain's genotype/phenotype and the host's genetic background.
- Specific H. pylori virulence factors (vacA, cagA) and their associated phenotypes (cytotoxin production, IL-8 induction) influence the host immune response and inflammatory potential.
- The study highlights the complexity of H. pylori pathogenesis and the need for strain-specific considerations in understanding and managing infections.
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