Using a genetically engineered mouse model, the team found that simply eradicating the infection-causing bug isn't enough to restore an animal's immune function. Lipopolysaccharide, or LPS, the dominant bacterial "signal" molecule that heralds the invasion, must also be inactivated. The findings are to appear online Sept. 11 in Cell Host & Microbe.
"We think this is the first evidence that killing the causative agent of a bacterial infection isn't enough for an animal to recover fully," said Dr. Robert Munford, professor of internal medicine and microbiology, and senior author of the study. "You've got to get rid of this molecule that the host is responding to or else its immune system remains suppressed."
By sensing and responding to LPS, animals mobilize their defenses to attack and kill the bacteria. This immune response also causes inflammation in the host. For a few days after the infection begins, however, an animal's ability to sense the bacteria is turned down, presumably to prevent further inflammation. In the current study, the researchers found that mice didn't recover from this "tolerant" period unless the LPS was inactivated by acyloxyacyl hydrolase, an enzyme discovered in 1983 by Munford and Dr. Catherine Hall, now an assistant professor of internal medicine at UT Southwestern.