Host DNA can trigger inflammation, study finds

By Laurie Wang

A new study at the University of Calgary reveals how the immune system triggers inflammation.
Published in the prestigious scientific journal Nature, the research aims to enhance treatments for people with lupus, kidney failure, heart disease, arthritis and inflammatory bowel disease.

“These findings are a huge step forward in basic research into inflammation,” says Dr. Daniel Muruve, associate professor of medicine in the University of Calgary’s Faculty of Medicine.

Muruve, a kidney specialist with the Calgary Health Region, along with collaborators at the University of Lausanne in Switzerland, have discovered a pathway in the cell that recognizes host DNA. When the DNA activates this pathway, inflammation occurs.

This research began as an exploration into how the immune system responds to the common cold virus. Muruve’s team introduced the virus into the cell and observed that the viral DNA triggered inflammation. That discovery prompted the team to investigate whether the cell’s own DNA would have the same effect.

“We found that it did,” says Muruve. “The immune system detects the DNA as a distress signal and then triggers inflammation,” he explains.

Published online in the international journal Nature, the U of C study is the first to prove that there is a pathway that can detect the cell’s own DNA. Previous scientific studies have identified pathways sensing foreign DNA - that of bacteria and viruses.

This research raises the possibility that lupus, a disease in which the immune system attacks healthy tissues, might involve a malfunction of the body’s own DNA. These findings are also expected to help researchers find ways to limit the inflammatory response in kidney disease, stroke, heart disease and inflammatory bowel disease.

“The next phase of our research will look at how this pathway might contribute to diseases such as lupus, kidney disease and colitis,” Muruve says. “Our goal is to take this fundamental discovery and translate what we’ve learned into clinical research.”

A member of the Institute of Infection, Immunity, and Inflammation, Muruve is a scholar with the Alberta Heritage Foundation for Medical Research, and is supported by the Canadian Institutes of Health Research.