"Scientists are beginning to suspect that keystone pathogens might be playing a role in irritable bowel disease, colon cancer and other inflammatory diseases," Hajishengallis said. "They're bugs that can't mediate the disease on their own; they need other, normally non-pathogenic bacteria to cause the inflammation."
In this study, they wanted to more fully understand the molecules involved in the process by which P. gingivalis caused disease.
"We asked the question, how could bacteria evade killing without shutting off inflammation, which they need to obtain their food," Hajishengallis said.
The researchers focused on neutrophils, which shoulder the bulk of responsibility of responding to periodontal insults. Based on the findings of previous studies, they examined the role of two protein receptors: C5aR and Toll-like receptor-2, or TLR2.
Inoculating mice with P. gingivalis, they found that animals that lacked either of these receptors as well as animals that were treated with drugs that blocked these receptors had lower levels of bacteria than untreated, normal mice. Blocking either of these receptors on human neutrophils in culture also significantly enhanced the cells' ability to kill the bacteria. Microscopy revealed that P. gingivalis causes TLR2 and C5aR to physically come together.
"These findings suggest that there is some crosstalk between TLR2 and C5aR," Hajishengallis said. "Without either on
|Contact: Katherine Unger Baillie|
University of Pennsylvania