Typhoid fever is characterized 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
), which normally infects humans but not mice. Unlike humans, mice express toll-like receptor 11 (TLR11), an immune cell receptor that recognizes molecules found in a range of microbes and triggers immune responses that help to fight infections.
"The two vaccines currently approved for this disease are only modestly effective, so research aimed at improving vaccines is essential," says senior study author Sankar Ghosh of Columbia University.
Because TLR11 is highly expressed in the mouse intestine, Hayden and his colleagues suspected that this receptor might recognize 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. But 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 recognized by TLR11. Because 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 says.
Source: Eurekalert
