Natural History of Helicobacter hepaticus Infection in Conventional A/J Mice, with Special Reference to Liver Involvement

Abstract

It has been reported that Helicobacter hepaticus infection of mice leads to chronic hepatitis and hepatocarcinoma. Our aim was to monitor a cohort of 80 conventional A/J mice in which half of the mice were infected by H. hepaticus in order to study the evolution of the infection and the pathological changes in comparison to uninfected mice. H. hepaticus was detected by culture only in some colon and cecum specimens after 17 months of age, while PCR detected H. hepaticus in the intestines of all inoculated mice after only 5 months of infection. The percentage of mice in which H. hepaticus was detected in the gallbladder, bile ducts, and liver by PCR, as well as the number of bacteria present in the liver, tended to increase with increasing age and longer infection time. Anti-H. hepaticus immunoglobulin G antibodies were positive by enzyme-linked immunosorbent assay only in inoculated mice. Pathological findings were also more frequent as the mice grew older: fibrosis was present (especially in the peripheral part of the liver), and significant portal inflammation including lymphoid nodules was present in almost all infected animals. Biliary lesions of neutrophilic acute cholangitis or lymphocytic cholangitis were noted. However, lesions were also observed in uninfected animals, although at a significantly lower level, and the only hepatocellular carcinoma occurred in an uninfected mouse. The evolution towards hepatocarcinoma is not always the endpoint and may depend on the bacterial strain and on the environmental conditions.Helicobacter species are responsible for chronic infections. In humans, Helicobacter pylori induces gastritis, which may last for decades and may be a lifelong condition. This infection is the first bacterial infection found to be involved in the development of a carcinogenic process in humans (8).After the occurrence of an unexpected and high level of hepatocellular tumors in mice with chronic active hepatitis, H. hepaticus was cultured from the liver and identified as a new species of Helicobacter that induces carcinoma (5). This bacterium has been the topic of extensive research since then. There have been studies on diagnostic methods (4, 13, 16, 17), pathogenic properties (2, 18), and the process of carcinogenesis (3, 9, 15) but few prospective studies of the natural history of H. hepaticus infection and liver pathology in mice. Therefore, our aim was to study the natural history of this infection for 17 months and to use the LightCycler methodology to quantitate the bacteria present in the liver.Study design. Eighty male A/J mice (3 to 4 weeks old) (not specific pathogen free), obtained from Jackson Laboratory (Bar Harbor, Maine), were maintained in microisolator cages and fed conventional food (Usine d'Alimentation Rabonnelle, Villemoisson-sur-Orge, France). The mice were cared for in accordance with the National Institutes of Health guidelines. Half of the mice were orally inoculated with H. hepaticus (group I), and the other half (group II) were used as controls. H. hepaticus type st...

Neoplastic and Nonneoplastic Lesions in Aging Mice of Unique and Common Inbred Strains Contribution to Modeling of Human Neoplastic Diseases

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Helicobacter hepaticus catalase shares surface-predicted epitopes with mammalian catalases

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Helicobacter hepaticus Hydrogenase Mutants Are Deficient in Hydrogen-Supported Amino Acid Uptake and in Causing Liver Lesions in A/J Mice

“…Hence, we performed a real-time PCR to quantify H. hepaticus in the tissues (7,8). In addition, real-time PCR is a rapid and sensitive technique which has been used to amplify and detect H. hepaticus DNA from tissue isolates of infected mice (1,2,32). After homogenization of the liver and cecum, the DNA was extracted from 25 mg of the tissue by using the DNeasy tissue kit (QIAGEN).…”