The first mouse model of typhoid fever could help in creating more potent vaccines against the deadly pathogen. The model was developed by an Indian-American microbiologist and colleagues.
"The two vaccines currently approved for this disease (typhoid) are only modestly effective, so research aimed at improving vaccines is essential," says senior study author Sankar Ghosh of Columbia University.
Ghosh did his M.Sc from the University of Calcutta and MS and Ph.D from Albert Einstein College of Medicine, New York (Yeshiva University).
"Prior to our work, there was no small animal model for studying immune responses to the bacteria that cause typhoid fever," says study co-author Matthew Hayden of Columbia. "We hope that the model we have developed will promote rapid progress in developing better vaccines," the journal Cell reports.
Typhoid fever is characterised by rashes and severe diarrhoea. It causes over 220,000 deaths each year, mostly in developing countries lacking clean sources of drinking water.
It is caused by the bacterium Salmonella typhi (S. Typhi), which normally infects humans but not mice, according to a Columbia statement.
Unlike humans, mice express TLR11, an immune cell receptor that recognises molecules found in a range of microbes and triggers immune responses that help to fight infections.
Because TLR11 is highly expressed in the mouse intestine, Hayden and his colleagues suspected that this receptor might recognise pathogens that cause intestinal diseases and could be responsible for preventing typhoid fever in mice.
To answer these questions, the researchers inactivated the TLR11 gene in mice and exposed them to S. Typhi.
Exposed mice developed severe intestinal tissue damage and hallmark symptoms like fever and diarrhoea. But when the mice were first immunised with heat-killed S. Typhi, they mounted strong immune responses and became impervious to infection.
"Having an animal model vastly improves our ability to investigate diseases, the immune response and, importantly, can be immensely beneficial for efforts to develop new vaccines and therapies," Hayden says.