Animal models are precious tools in translational research if their predictive value to human disease is high enough. In the case of typhoid fever, infection of immunodeficient mice by Salmonella Typhimurium has been used for decades to simulate human infection by S. Typhi. Aside from permitting the study of Salmonella interaction with the animal host without the constraints and the dangers of working with a highly pathogenic species, the mouse model has provided a wealth of information on Salmonella virulence mechanisms. However, the steadily growing list of discrepancies between S. Typhimurium and S. Typhi infection mechanisms illustrates the limitations of the immunodeficient mouse model. In medical practice, the limited efficacy of existing typhoid fever vaccines further illustrates such shortages. In this scenario, breakthroughs may require the introduction of novel models like the human biopsy cultures and organoids used in the study discussed in this editorial. Organoids may be especially appropriate to study infection, immunity, and inflammation as they provide a source of human tissue that accurately reflects human responses.
Click here to view the article, published in Annals of Translational Medicine.