Schlesinger's lab has discovered that the most common strain of TB bacteria has evolved over time to make itself particularly attractive to the macrophages in the lungs. The mannose, or sugar, on the surface of these bacteria is the same mannose that the human body produces when it makes new proteins.
"When we make new proteins and they get into circulation and end up where they don't belong, we have mannose receptors that exist primarily to scavenge unwanted mannose proteins that we make without activating the innate immune system. It's a receptor to keep humans healthy," Schlesinger said.
It turns out that macrophages in the lungs have high activity of this mannose receptor.
"So the TB coats itself with sugars like decorating the branches of a Christmas tree, and that allows it to avoid an inflammatory response by slipping into the macrophage through this scavenger receptor," Schlesinger said.
During his presentation in Colombia, Schlesinger also described the related work that he and colleagues recently reported in the Journal of Biological Chemistry. The research team has identified two different strains of TB from ill patients that interact completely differently with macrophages. These strains do not coat themselves with sugar, so they have a harder time finding their way into macrophages in the lungs, where they could cause latent infection. Instead, they use a more primitive pathway to enter the macrophages, so fewer bacteria enter the lungs.
"We believe that these strains haven't been living in humans for very long, so they don't know how to get into their niche and sleep into latency, which is the most commonly seen TB behavior," Schlesinger said. "But the few bacteria that do get into the lung macrophages grow like gangbusters, and we speculate that this is one reason for why they are a cause of TB outbreaks."
|Contact: Larry Schlesinger|
Ohio State University