Experimental Helicobacter pylori infection induces antral gastritis and gastric mucosa-associated lymphoid tissue in guinea pigs

Abstract

Humans infected with Helicobacter pylori have abnormally low levels of the antioxidant vitamin C, which protects against the formation of carcinogenic nitrosamines, in gastric juice. Guinea pigs, like humans and nonhuman primates, have a dietary requirement for vitamin C. As such, these species have gastrointestinal vitamin C transport systems not found in other animals. We have developed and characterized a guinea pig model of chronic gastric H. pylori infection with the rodent-adapted Sydney strain of H. pylori. At 4 weeks postinfection, five of six animals of the infected group and zero of two animals of the control group were positive for H. pylori as determined by culture or PCR. At 15 weeks, six of six animals of the infected group and zero of two animals of the control group were positive. H. pylori-specific seroconversion was observed among infected animals. There were no histologic abnormalities in the gastric antra or fundi of control guinea pigs. In contrast, there was multifocal, mild to moderate lymphohistiocytic antral gastritis and formation of antral lymphoid follicles in H. pylori-infected animals. The lesion distribution in the gastric antra paralleled that observed in H. pylori-infected humans. The H. pylori-infected guinea pig should prove useful in modeling the interaction of helicobacter and vitamin C in gastric carcinogenesis.

FIG. 1

H. pylori serology. OD readings are plotted versus individual guinea pig serum samples analyzed in duplicate. The cutoff line is the mean plus 3 SD of the OD readings of sham-dosed control guinea pigs at 4, 7, 12, and 15 weeks postdosing. One-third of the infected guinea pigs were seropositive at 4 weeks postinfection. OD readings for each of the six 15-week infected guinea pigs at 7, 12, and 15 weeks postinfection are plotted. One animal remained seronegative for the 15-week duration of the study. (Inset) To determine whether seropositivity correlated with active infection or merely with exposure to H. pylori antigen, three adult female guinea pigs (A, B, and C) were dosed with killed H. pylori antigen, following the same dosing schedule and receiving the same quantity of antigen as the experimentally infected group. The cutoff line is the mean plus 3 SD of the OD readings from these guinea pigs prior to dosing. Two of the three guinea pigs were borderline seropositive at 4 weeks but seronegative at 5 weeks postexposure (a decreasing titer), in contrast to the H. pylori-infected guinea pigs, who had rising titers for the duration of their infection. ∗, sample unavailable.

FIG. 2

Experimental H. pylori infection causes antral gastritis in the guinea pig. There were no abnormalities in the gastric antra or fundi (not shown) of the control sham-dosed guinea pigs at either 4 or 15 weeks after dosing (a). At 4 weeks (b) and 15 weeks (c) there was a moderate lymphohistiocytic, eosinophilic infiltrate in the submucosa and deep mucosa, with multifocal extensions to the superficial mucosa (arrows). The inset illustrates eosinophils. Active inflammation characterized by heterophilic infiltrate (guinea pig polymorphonuclear phagocytes) was present in the mucosa in scattered foci. At 4 weeks postinfection, the infiltrate was concentrated in the corpus-antrum junction, and at 15 weeks postinfection it extended throughout the antrum. H&E stain was used. Bar = 150 μm.

FIG. 3

Experimental H. pylori infection induces formation of gastric mucosa-associated lymphoid tissue in the guinea pig. At 4 weeks postinfection, lymphoid infiltrates formed multifocal aggregates in the deep mucosa (a) and submucosa (b). The inset illustrates lymphocytes. At 15 weeks postinfection (c), lymphofollicular organization was prominent. The follicles were large (note scale bar), had prominent germinal centers (G), and featured hyperplastic ingrowth of the overlying mucosal epithelium. H&E stain was used. Bar = 150 μm.