The immune system remembers. Often this memory, primed by past encounters with threats like bacteria or viruses, is an asset. But when that memory is sparked by internal drivers, like chronic inflammation, it can prove detrimental, perpetuating a misguided immune response. In a new paper in Cell, researchers from the Penn Dental Medicine, together with an international team at the Technical University of Dresden, lay out the mechanism by which innate immune memory can cause one type of inflammatory condition—in this example, gum disease—to increase susceptibility to another—here, arthritis—through alterations to immune cell precursors in the bone marrow.
In a mouse model, the team demonstrated that recipients of a bone marrow transplant were predisposed to more severe arthritis if their donor had inflammatory gum disease.
“Although we use periodontitis and arthritis as our model, our findings go beyond these examples,” says George Hajishengallis, a professor at Penn Dental Medicine and a corresponding author on the work. “This is in fact a central mechanism—a unifying principle underlying the association between a variety of comorbidities.”
The researchers note that this mechanism may prompt a reconsideration of how bone marrow donors are selected, as donors with certain types of immune memory caused by underlying inflammatory conditions might put bone marrow transplant recipients at a higher risk of inflammatory disorders.
The work also underscores that blocking IL-1 receptor signaling could be an effective approach to mitigate against these knock-on effects of trained immunity.
Further experiments suggested that the signaling pathway governed by a receptor for the molecule IL-1 played a vital role in contributing to this inflammatory memory. Mice that lacked IL-1 receptor signaling could not generate the immune memory that made the recipient mice more susceptible to comorbidities, the researchers found.
“We’ve seen anti-IL-1 antibodies used in clinical trials for atherosclerosis with excellent results,” Hajishengallis says. “It could be that it was in part because it was blocking this maladaptive trained immunity.”
Follow-up projects are examining how other inflammatory conditions may be linked with periodontal disease, a sign, the researchers say, of how crucial oral health is to overall health.
“I’m proud for the field of dentistry that this work, with significance to a wide range of medical conditions, began by investigating oral health,” Hajishengallis says.