Helicobacter rodentium was first recognized as a potential pathogen when it was isolated, along with Helicobacter bilis, from a colony of scid/Trp53 knockout mice with diarrhea. Clinical disease in these mice was more severe than that previously reported in mice infected with H. bilis alone, thus suggesting that H. rodentium contributed to the pathogenesis of enteritis. The purpose of the study reported here was to address two questions: is H. rodentium pathogenic in mice, and when co-infection with a pathogenic helicobacter occurs, does H. rodentium augment disease? To this end, A/JCr and C.B-17/IcrCrl-scidBr mice were inoculated with H. rodentium and/or H. hepaticus. Twelve weeks after inoculation, mice were euthanized. The cecum and liver were evaluated microscopically for evidence of disease. Cecal interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1α (MIP-1α), interleukin 10 (IL-10), and interferon gamma (IFN-) mRNA values were measured as an indicator of mucosal immune response. Hepatic lesions were not identified in mice mono-infected with H. rodentium; likewise, cecal lesion scores were not significantly different from those of uninfected controls. With the exception of an increased IL-10 mRNA value in SCID mice, mean immune-related gene expression in H. rodentium mono-infected and uninfected control mice was not significantly different. In contrast, all mice infected with H. hepaticus developed moderate to severe hepatitis, significant increase in cecal lesion scores, and increased immune-related gene expression. The C.B-17/IcrCrl-scidBr mice co-infected with H. hepaticus and H. rodentium had liquid cecal contents and low terminal body weight. Further, compared with mice infected with H. hepaticus alone, co-infection was associated with significant increases of IL-10, MIP-1α, and IP-10 mRNA values in C.B-17/IcrCrl-scidBr and IFN- and MIP-1α mRNA values in A/JCr mice. These results suggested that H. rodentium alone does not cause hepatitis or enteritis in A/JCr or C.B-17/IcrCrl-scidBr mice; however, co-infection with H. hepaticus and H. rodentium was associated with augmented cecal gene expression and clinical manifestation of disease in immunodeficient mice.
Research Animal Diagnostic Laboratory, Department of Veterinary Pathobiology, University of Missouri, Columbia, Missouri
Publication date: October 1, 2004
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Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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