Most of what scientists know about how Salmonella causes disease comes from studying a strain called Salmonella typhimurium, which can infect both mice and humans.
However, Fang noted that Salmonella infections in mice have not been found to correlate well with human typhoid infections.
"The mouse Salmonella infection differs from human typhoid in a number of important respects," he said. Immunity to one strain is fundamentally distinct from immunity to the other. This complicates attempts to construct vaccines based on observations of mice infected with Salmonella typhimurium."
Fang added that Salmonella typhi, the cause of human typhoid fever, is highly adapted to people. It has evolved many ways to evade infection-fighting defenses inside humans. It can also enter and destroy disease-fighting cells. The bacteria induce inflammation where it is in their own self-interest, and suppress it when and where it might be a disadvantage, such as in the intestine. Salmonella has changed over time by acquiring new DNA, such as plasmids and bacteriophages, from other organisms. This borrowed DNA makes it more virulent to humans and other animal hosts.
The host-pathogen interactions in mouse typhoid and human typhoid fever are drastically removed from each other, Fang said.
The researchers demonstrated that human blood-forming cells engrafted into immune-deficient mice allowed the mice to be infected with the organism that causes human typhoid fever, and that the typhoid bacteria appeared to reproduce inside the human cells. The researchers were also able to use this model to look for genetic factors that the typhoid bacteria need to cause severe illness.
Based on their studies, the researchers believe that the new lab mouse model can provide an unprecedented opportunity to gain insights into how the human t
|Contact: Leila Gray|
University of Washington