Scientists led by an Indian-American microbiologist have developed the first mouse model of typhoid fever that could help in creating more effective vaccines against the deadly pathogen.
Researchers from the Columbia University found that since mice show human-like symptoms and respond positively to immunization, they could be used to develop more effective vaccines against the common bacterial disease.
Typhoid fever is characterised by rash and severe diarrhea, and it causes more than 220,000 deaths each year, frequently 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. Unlike humans, mice express toll-like receptor 11 (TLR11), an immune cell receptor that recognises molecules found in a range of microbes and triggers immune responses that help to fight infections.
"Prior to our work, there was no small animal model for studying immune responses to the bacteria that cause typhoid fever," said study author Matthew Hayden.
"We hope that the model we have developed will promote rapid progress in developing better vaccines," Hayden said.
"The two vaccines currently approved for this disease are only modestly effective, so research aimed at improving vaccines is essential," said senior study author Sankar Ghosh.
Since TLR11 is highly expressed in the mouse intestine, researchers 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. These mice developed severe intestinal tissue damage and hallmark symptoms such as fever and diarrhea.
When the mice were first immunized with heat-killed S Typhi, they mounted strong immune responses and became impervious to infection.
Moreover, the researchers found that the key component responsible for S Typhi's virulence is a protein called flagellin, which is recognised by TLR11.
Since other pathogens have flagellin, these mice might also serve as a model system for other important bacterial diseases.
"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 said in a statement.
The study was published in the journal Cell.