Disease-fighters in our mouths provide clues to enhancing the immune system

Studies of natural antibiotics in our mouths may lead to new treatments for oral infections, as well as ways to boost the infection-fighting powers of mouthwashes, denture coatings, and wound dressings, according to a presentation at the annual meeting of the American Association for the Advancement of Science (AAAS). These compounds, called beta-defensins, are key components of our innate immune system.

“Innate immunity describes the defenses that we’re are born with; they’re coded in our genes. In contrast, we develop the antibodies of our acquired immune system over time as we’re exposed to bacteria and viruses,” said Dr. Beverly Dale, professor in the University of Washington Department of Oral Biology, School of Dentistry, and scientific director of the UW Comprehensive Center for Oral Health Research. “It’s when our innate defenses fail that the acquired immune system picks up the slack.”

The innate immune system has some remarkable characteristics, including the ability to distinguish between harmless and harmful bacteria. For example, disease-causing and harmless, or commensal, bacteria trigger the activation of beta-defensins through different chemical signaling pathways. The role of commensal bacteria may be to alert the immune system to the possible presence of invading bacteria, according to Dale.

The mouth is “a perfect place to study the innate immune system because it’s such an incredibly complex and challenging ecological system,” Dale said. “Our mouth is full of moist surfaces, perfect for bacteria to adhere to; we feed these bacteria at regular intervals with nutritious foods and snacks.” As a result, and despite efforts to brush them away, we have millions of bacteria in our mouths, according to Dale. “Yet most of us remain healthy–without infections–most of the time.”

Dale and colleagues from the Comprehensive Center for Oral Health Research, Dr. Richard Darveau of the departments of Periodontics and Oral Biology, and Dr. Edward Clark of the Department of Microbiology, School of Medicine, will join Dr. David Relman of Stanford University’s departments of Microbiology & Immunology, and Medicine for a 12:30 p.m. session Monday, Feb. 16, on “Innate Immunity and Oral Health” at the AAAS’s annual meeting in Seattle.

Knowledge of the ways harmful and harmless bacteria interact with our immune systems has been limited by the fact that many kinds of bacteria won’t grow in a laboratory. Relman has developed high-throughput methods to better analyze oral microbial communities and will discuss his results in the session “Microbial Diversity and Oral Health.”

The microorganisms in our mouths are most obvious when they collect on our teeth as plaque, a tough sticky mixture that can contain over 300 species of bacteria. Most of these bacteria are harmless commensals, but a minority, such as the bacteria Porphyromonas gingivalis, can cause periodontal or gum disease. Darveau’s session will include an overview of innate immunity and how is it affected by the presence of disease-causing bacteria, such as P. gingivalis.

Special receptors on sentinel cells may help them detect invading pathogens. Clark’s session will discuss how these sentinels activate both the innate and acquired immune systems.

In her session on beta-defensins, Dale will discuss the ways that these natural antibiotics are activated and could be used to treat or prevent infection. Some institutions are already testing the use of simple antimicrobial peptides similar to beta-defensins to prevent oral mucositis, an infection that is a side effect of some chemotherapy treatments. Other possible uses for beta-defensins, or natural compounds that stimulate their production, may include mouthwashes, denture coatings, wound dressings, and coatings for catheters and other medical equipment.

“The innate immune system is a very subtle system that keeps us healthy most of the time,” Dale said. A better understanding how the system works can help us understand how to enhance it, she said: “If our cells can tell the difference between different types of bacteria, what else are they doing that may protect our bodies from infection?”

The work of Dale, Darveau, and Clark was funded by the National Institute of Dental and Craniofacial Research (NIDCR).