"We think bacteria might be exporting citrate because it would otherwise prevent the bacteria from growing," Brodsky said. "It's possible that the export of citrate might be triggering the inflammatory response. Our work fits into this emerging idea that bacterial metabolites might be recognized by various components of the immune system for the purpose of either negatively or positively regulating immune responses."
The scientists believe that it's possible that host cells put together two pieces of information to trigger an immune response, first recognizing signaling of a Toll-like receptor, which responds to structures that are common across many microbes, and then sensing bacterial products, like elevated levels of citrate, being produced inside the cell itself.
Brodsky and colleagues are now working to develop a chicken vaccine based on an attenuated strain of Salmonella that would trigger both "arms" of the inflammatory response, possibly involving an aconitase mutant. Such a vaccine would ideally more closely replicate a natural infection, protecting the animals against infection.
"We get Salmonella from chickens that are chronically infected," Brodsky said, "so, if you could prevent or limit chronic infection of chickens, that would be a nice way to limit Salmonella in the food supply."
|Contact: Katherine Unger Baillie|
University of Pennsylvania