Immune Responses of Specific-Pathogen-Free Mice to Chronic Helicobacter pylori (Strain SS1) Infection

Abstract

A model permitting the establishment of persistentHelicobacter pylori infection in mice was recently described. To evaluate murine immune responses to H. pylori infection, specific-pathogen-free Swiss mice (n = 50) were intragastrically inoculated with 1.2 × 107 CFU of a mouse-adapted H. pylori isolate (strain SS1). Control animals (n= 10) received sterile broth medium alone. Animals were sacrificed at various times, from 3 days to 16 weeks postinoculation (p.i.). Quantitative culture of gastric tissue samples from inoculated mice demonstrated bacterial loads of 4.0 × 104 to 8 × 106 CFU per g of tissue in the animals. Infected mice had H. pylori-specific immunoglobulin M (IgM) and IgG antibodies in serum (at day 3 p.i.) and IgG and IgA antibodies in their gastric contents (weeks 4 and 16 p.i.) and saliva (week 16 p.i.). Mucosal IgM antibodies were not detected. Histological examination of the gastric mucosae from control and infected mice revealed mild chronic gastritis, characterized by the presence of polymorphoneutrophil cell infiltrates and submucosal lymphoid aggregates, in infected animals at 16 weeks p.i. Differences in the quantities of IgG1 and IgG2a subclass antibodies detected in the sera of mouse strains (Swiss, BALB/c, and C57BL/6) infected by H. pylori suggested that host factors influence the immune responses induced against this bacterium in the host. In conclusion, immune responses to H. pylori infection in mice, like those in chronically infected humans, appear to be ineffective in resolving the infection.

Reduced activation of inflammatory responses in host cells by mouse-adapted Helicobacter pylori isolates

“…The mean bacterial loads for these animals varied from 3.08 log cfu g -1 gastric tissue to a maximum mean load per group of 5.59 ± 0.42 log cfu g -1 tissue ( Table 1). Two of the cagA -/non-NF-kB-activating input isolates (strains 189 and 240) colonized Swiss mice to similar levels to those reported previously for the mouse-adapted H. pylori SS1 strain (Lee et al, 1997;Ferrero et al, 1998). In contrast, four out of six cagA + /NF-kB-activating H. pylori isolates (strains 244, 246, 247 and 251) were incapable of establishing an infection in mice, including one isolate (strain 246) that had been identified in the initial screening experiment as being a potential mouse-colonizing strain.…”

“…Helicobacter pylori isolates that do not activate NF-kB in epithelial cells are better adapted to colonize mice Helicobacter pylori isolates were randomly screened for the ability to colonize Swiss mice. This mouse strain was shown previously to be highly sensitive to H. pylori infection (Ferrero et al, 1998;Ferrero and Jenks, 2001). Groups of three mice were each inoculated twice, on alternate days, with one of the 12 'input' strains characterized above (Table 1).…”

“…Although several H. pylori animal models successfully mimic the severity and types of inflammatory lesions associated with human disease, mice infected with H. pylori strains develop relatively mild forms of gastritis (Ferrero et al, 1998;van Doorn et al, 1999;Smythies et al, 2000). Researchers were initially unable to establish H. pylori infections in mice; however, subsequent studies showed that human H. pylori isolates could be adapted to this host through mouse-to-mouse passage (Marchetti et al, 1995;Lee et al, 1997).…”

“…Researchers were initially unable to establish H. pylori infections in mice; however, subsequent studies showed that human H. pylori isolates could be adapted to this host through mouse-to-mouse passage (Marchetti et al, 1995;Lee et al, 1997). One of these mouse-adapted isolates, the H. pylori SS1 strain, was shown to colonize mouse gastric mucosa with high bacterial numbers and for extended periods of time (Lee et al, 1997;Ferrero et al, 1998). The H. pylori SS1 strain was described as having a cagA + genotype and was isolated from an individual with a history of severe H. pylori-related disease (peptic ulceration) (Lee et al, 1997).…”

“…The H. pylori SS1 strain was described as having a cagA + genotype and was isolated from an individual with a history of severe H. pylori-related disease (peptic ulceration) (Lee et al, 1997). Nevertheless, this strain induced a relatively low-grade inflammation in mice, particularly during the early stages of infection, when compared with other Helicobacter infection models (Lee et al, 1997;Ferrero et al, 1998;van Doorn et al, 1999). Thus, we speculated that the host adaptation procedure had attenuated the ability of H. pylori SS1 to induce inflammation in the murine host.…”