Chronic Atrophic Gastritis in SCID Mice Experimentally Infected withCampylobacter fetus

Abstract

Campylobacter fetus is a cause of enteritis and invasive extraintestinal disease in humans. In order to develop an animal model of C. fetus infection, outbred ICR SCID mice were orally challenged with a clinical isolate of C. fetus. The stomachs of SCID mice were heavily colonized with C. fetus, and colonization was associated with the development of chronic atrophic gastritis. This lesion was characterized by an inflammatory infiltrate of granulocytes and macrophages that over time resulted in a loss of specialized parietal and chief cells in the corpus and the appearance of a metaplastic mucous epithelium. This lesion bears similarity to that encountered during experimental murine infection with Helicobacter pylori or Helicobacter felis. Despite colonization of the cecum and colon tissues by C. fetus in SCID mice, no lesions were noted in these tissues. A follow-up study confirmed these findings for SCID mice and also demonstrated that C. fetus could also infect the gastric mucosa of wild-type, outbred ICR mice. However, in ICR mice, the anatomic extent of colonization was more limited and the severity of inflammation and epithelial alterations was significantly less than that observed in infected SCID mice. The stomach may represent an unrecognized environmental niche for Campylobacter species.

Mice Lacking T and B Lymphocytes Develop Transient Colitis and Crypt Hyperplasia yet Suffer Impaired Bacterial Clearance during Citrobacter rodentium Infection

“…Thus, the gradual increase in tissue pathology and bacterial clearance seen in wild-type mice was consistent with the activation of acquired immunity during infection. However, the transient nature of the host response to C. rodentium infection seen in the RAG1 KO mice was surprising, because infection of RAG1 KO mice by other bacterial pathogens usually leads to prolonged inflammatory responses (31,56,61). Whether the attenuation of the host response in the RAG1 KO mice is host or bacterial driven is uncertain.…”

Campylobacter jejuniColonization of Mice with Limited Enteric Flora

“…However, in virtually all studies, oral inoculation of wild-type mice results in sporadic intestinal colonization and an absence of intestinal disease. Interestingly, published experimental infections of immunocompromised mice demonstrate more efficient colonization and sporadic intestinal pathology (20,25,51,53,54).…”

“…Discrepant results using mice as an experimental model have appeared in the literature over the past 20 years and are likely due to the use of different Campylobacter strains and inoculum sizes to infect diverse murine strains with varied gut flora complexity and immune repertoires. While some groups reported efficient colonization of normal flora mice by high oral doses of Campylobacter (8,10,25,51), our results more closely reflect studies showing robust colonization only in a gut environment with decreased microbial diversity, as in germfree (27,53,54), neonatal (19), or antibiotic-treated mice (18). Colonization persistence has been less thoroughly tracked in these reports, although continued excretion of Campylobacter from both normal and immunocompromised mice for up to 2 months was shown (10,20,25).…”

“…Murine models of C. jejuni infection overcome some of these limitations, but available models suffer from sporadic colonization or an absence of consistent intestinal pathology or clinical signs (8,10,27). The use of germfree/gnotobiotic or immunocompromised mice has alleviated these shortcomings with varying degrees of success (25,51,53,54). However, to date no particular model has been broadly and consistently employed to study Campylobacter infection and immunity in mammals.…”

Gastroenteritis in NF-κB-Deficient Mice Is Produced with Wild-TypeCamplyobacter jejunibut Not withC. jejuniLacking Cytolethal Distending Toxin despite Persistent Colonization with Both Strains

“…(i) Preparation of cell sonicates. Bacteria were grown on blood agar plates (Remel) under microaerobic conditions, and sonicates were prepared as previously described (41). Sonicates were stored at Ϫ70°C until they were used.…”