Two‐year follow‐up of Helicobacter pylori infection in C57BL/6 and Balb/cA mice

Abstract

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. We previously found high‐grade lymphoma after 13 months' H. pylori infection in C57BL/6 mice. In this study we followed H. pylori infection by three different isolates in C57BL/6 and Balb/cA mice for 23 months. Six‐week‐old C57BL/6 and Balb/cA mice were infected with H. pylori strains 119p (CagA+, VacA+), SS1 (CagA+, VacA+) and G50 (CagA‐, VacA‐). Mice were followed at 2 weeks, 10 weeks and 23 months post‐inoculation (p.i.) by culture, histopathology and serology. Strain G50 was only reisolated from mice 2 weeks p.i. There was no difference in colonization between strain 119p and SS1 at 10 weeks p.i., whereas SS1 gave 100% colonization versus 119p gave 50% 23 months p.i.. Interestingly, the inflammation score was higher in mice infected with strain 119p than with SS1 10‐week p.i., and there were lymphoepithelial lesions in mice infected with strain 119p and G50 but not with SS1 at 23 months post‐infection. Eight mice infected with strains 119p and G50 developed gastric lymphoma (grade 5 and 4). One C57BL/6 mouse infected with strain 119p developed hepatocellular carcinoma after 23 months. Immunoblot showed specific bands of 26–33 kDa against H. pylori in infected mice, and two mice infected with strain SSI reacted with antibodies to the 120 kDa CagA toxin. Conclusion: A reproducible animal model for H. pylori‐induced lymphoma and possibly hepatocellular carcinoma is described. Strain diversity may lead to different outcomes of H. pylori infection.

Development of a BALB/c mouse model of Helicobacter pylori infection with fresh and frozen bacteria

“…In contrast with these studies, other authors have demonstrated that the clinical outcome of H. pylori infection is independent of cagA and vacA expression in humans (Yamaoka et al, 1999) as well as in mice (Ayraud et al, 2002;Wang et al, 2003). Our data confirm these findings as the strain we used in our model was confirmed as cagA + and vacA + by PCR, and inoculated animals did not develop marked gastritis or peptic ulcers.…”

Galectin-3 Plays an Important Role in Innate Immunity to Gastric Infection by Helicobacter pylori

“…This may be related to the pathogenesis of MALT lymphoma in humans by chronic H. pylori colonization (41). The results may also be remarkable in that a previous study observed no MALT lymphoma formation in WT mice infected with H. pylori Sydney strain 1 even after the 2-year follow-up period (42). Thus, Gal3-deficient mice may provide a useful model for the study of MALT lymphomagenesis by colonization with H. pylori Sydney strain 1 (43,44).…”

Expressions of the CagA protein and CagA-signaling molecules predict Helicobacter pylori dependence of early-stage gastric DLBCL

“…69,70 In a generated CagA transgenic mouse model, Ohnishi et al provided direct evidence of CagA acting as a bacterial oncoprotein in the growth of HP-related DLBCL through a tyrosine phosphorylation-dependent SHP-2-ERK signaling pathway. 71 Using in vitro B-cell line models, we and other investigators have demonstrated that translocated CagA can stimulate proliferation and restrain the apoptosis of B cells through ERK activation, BAD phosphorylation, p53 accumulation, BAD phosphorylation, or upregulation of Bcl-2 and Bcl-XL expression.…”