Next, they profiled the genes that were expressed in immune cells called macrophages isolated from the antibiotic-treated mice. These data revealed a decreased expression of genes associated with antiviral immunity. In addition, macrophages from antibiotic-treated mice showed defective responses to interferons, proteins made and released in response to viruses, bacteria, parasites, or tumor cells. Under normal circumstances, interferons facilitate communication between cells to trigger the immune cells that attack pathogens or tumors. The antibiotic-treated mice also had an impaired capacity to limit viral replication. However, when mice were treated with a compound that restored interferon responsiveness, protective antiviral immunity was re-established.
"It is remarkable that signals derived from one type of microbe, in this case bacteria, can have such a profound effect on immune responses to viruses that are a very different type of microbe," says first author Abt. "Just like we would set a thermostat to regulate when a heater should come on, our studies indicate that signals derived from commensal bacteria are required to set the activation threshold of the immune system."
Taken together, these lines of evidence indicate that signals from commensal bacteria beneficially stimulate immune cells in a way that is optimal for antiviral immunity. "Although more work needs to be done, these findings could illuminate new ways to promote better immunity to potentially life-threatening viral infections," adds Artis.
|Contact: Karen Kreeger|
University of Pennsylvania School of Medicine