Animal models of Campylobacter jejuni colonization and disease and the lessons to be learned from similar Helicobacter pylori models

The mechanisms by which Campylobacter jejuni induces disease in human beings remain unknown. Identification of campylobacter virulence factors requires appropriate animal models. Several in vivo models of disease have been described. Models in non-human primates are closest to the disease in humans but are excluded on ethical grounds. An oral ferret model, inducing mild diarrhoea, has proved promising in the investigation of virulence factors but may be difficult to use widely. The same is true for piglet models. Rabbit models reported generally involve surgical intervention and abnormal routes of administration, and are consequently of limited accessibility and usefulness. Several mouse models have recently been described; one model with orally challenged SCID mice induced diarrhoea. However, the frequency of disease was low. Moreover, immune-compromized mice would have restricted usefulness for immunological studies. The use of alternative challenge routes in mice, such as via the nasal mucosa, may be of value if the effects are reproducible. In summary, models of campylobacteriosis remain unavailable. Acceptable models of colonization have been developed; the most frequently used is the orally challenged one-day-old chick. Identification of bacterial factors important in the colonization of chickens may lead to the development of targeted intervention strategies to reduce contamination of the food chain by this pathogen. However, the value of models of avian colonization to investigate human infection has yet to be established. Comparison of animal models of the related pathogens C. jejuni and Helicobacter pylori has been informative. Although faced with similar problems, acceptable animal models of several disease manifestations of H. pylori infection are now available. This experience suggests that appropriate models of campylobacteriosis can be developed. Approaches involving the manipulation of both the pathogen and host are suggested which may enable the virulence of C. jejuni to become detectable in animal models in the near future.