AUGUSTA, Ga. - A well-documented suppressor of immunity that's used by fetuses and tumors alike, just may be able to change its spots, researchers report.
In the face of a significant bacterial infection, for example, indoleomine 2,3-dioxegenase, or IDO, also appears capable of helping key immune cells called macrophages produce inflammation to destroy the invader, said Dr. Tracy L. McGaha, immunologist at the Medical College of Georgia at Georgia Regents University and GRU Cancer Center.
The surprising finding points toward new therapeutic targets when inflammation goes overboard, known as a cytokine storm, as with the overwhelming and highly lethal infection septicemia.
"It's always described as a one-way street, but it appears IDO has a dual role," said McGaha, corresponding author of the study in the journal Molecular and Cellular Biology. "It promotes inflammation when it needs to and, where there is no need for classic inflammation, it can immediately switch to a suppressant mechanism," McGaha said.
IDO's upregulation in macrophages helps these immune cells make important decisions about whether to ignore or attack. "It just depends on the environment the cell finds itself in," McGaha said. He and others also are showing that macrophages, well-documented garbage consumers in the body, have this larger role as well as a driver of the immune response.
While studying more about IDO's role in modulating macrophages response to cell debris, McGaha and his colleagues found that when they added a piece of a bacterial cell wall to prompt an inflammatory reaction, they found an increased number of IDO-expressing macrophages in the mix, which seemed counterintutitive considering IDO's role as a suppressor, McGaha said.
That's how they learned IDO actually does both. IDO basically works by degrading the essential amino acid tryptophan, producing a stress response in the now-starving cell that pro
|Contact: Toni Baker|
Medical College of Georgia at Georgia Regents University