Tooth decay may result from immune response, not just bacterial plaque

U of T researchers find evidence for maverick theory first published in 1970

Tooth decay may result from immune response, not just bacterial plaque

Cavities in teeth may result from an immune system response, not just bacteria, according to a recent U of T study. This counters decades of established thinking in dental research.

In 1970, Dr. John Gabrovsek of the Cleveland Clinic published research in the Journal of Dental Research that found that our immune system may contribute to dental cavities. But during the almost 50 years since it was published, most dental researchers have not taken Gabrovsek’s theory seriously — until U of T’s findings were published in April.

The research was spearheaded by Dr. Yoav Finer and Dr. Michael Glogauer, both professors at the U of T Faculty of Dentistry.

“Glogauer approached me a few years ago, [and] told me that these immune system cells have the same enzymes and more enzymes than bacteria have, so why not check them?” Finer explained to The Varsity.

The research team began by examining immune cells called neutrophils. Neutrophils are a type of white blood cell routinely found in the mouth, and they act as the first line of defense against harmful bacteria.

However, as these immune cells fight against harmful pathogens that can damage teeth, they can also cause collateral damage to what they are originally trying to protect — our teeth.

While bacteria still cause most of the damage that results in tooth decay, Finer explained that the research team has found evidence that these immune cells also contribute to cavity formation.

How the research team arrived at the discovery

Through years of study, the team created samples from extracted teeth and then used acid to remove minerals from them.

The application of acid mimicked the effect that harmful bacteria have on teeth, as the acid they release causes tooth decay.

The researchers then isolated neutrophils from human volunteers and kept them at a warm temperature with the extracted teeth.

“That was a daily procedure because you can’t culture these cells — neutrophils — unlike bacteria,” said Finer. “You need to get these cells isolated from the blood donors on a daily basis or every other day.”

The team found that while these immune cells help protect teeth from damage caused by bacteria, they can also remove minerals from tooth dentin, as well as break down white-coloured tooth fillings.

A possible explanation for why neutrophils can degrade teeth, according to Finer, is their enzymes — biological molecules that speed up chemical reactions. However, it remains unclear which type of enzyme could be responsible for contributing to dental decay.

Applications of the research findings

Protecting our teeth is important, as dental diseases can affect not just our mouths, but our overall health. For example, bacteria that cause gum disease can lead to infections of our lungs and increased risk of blockage in arteries that can damage our hearts.

Glogauer’s research team has been developing a mouth rinse that could prevent some of the degradation caused by these immune cells to apply the findings to clinical dentistry.

Finer’s research team has also been developing a dental varnish that contains anti-degradative factors to help counteract the effect of both bacteria and neutrophils on teeth.

However, preventing tooth decay ultimately comes down to maintaining good oral hygiene.

“With a recommended toothpaste and toothbrush, keeping good oral hygiene is the key,” explained Finer. “It’s our first line of defense and can eliminate a lot of problems… the immediate thing is making sure you keep your sugar consumption under control.”

Treating brain inflammation starts from the gut

Immune cells from the gut found to suppress brain inflammation

Treating brain inflammation starts from the gut

Researchers at U of T have found that immune cells from the intestine can be used to reduce brain inflammation in patients with multiple sclerosis (MS). When outside of the gut, these IgA-producing plasma cells attenuate disease symptoms within the central nervous system (CNS). IgA is an antibody commonly found in mucous membranes.

MS results in inflammatory lesions throughout the CNS, including the brain and spinal cord, disturb the transmission of electrical signals through nerves. The consequent symptoms vary from person to person, but often include impaired sensation, cognition, and coordination.

Studies have focused on preventing the formation of new inflammatory lesions. This involves depleting or suppressing the activity of immunoreactive plasma cells. These plasma cells originate as B cells but differentiate in response to the presence of an antigen, releasing antibodies that trigger the immune response and simultaneous inflammation.

Previous trials have examined the effects of suppressing B cells, as opposed to plasma cells. The depletion of B cells has been shown to prevent the formation of inflammatory CNS lesions. Contrarily, the neutralization of plasma cells has been shown to exacerbate the MS symptoms.

Due to these opposing results, U of T researchers, led by immunology professor Jennifer Gommerman, sought to understand the source and function of plasma cells in the CNS during the inflammatory response. Specifically, they examined IgA-producing plasma cells, due to the unexpected discovery that these cells reside in the brain and spinal cord during an MS-like attack.

The researchers found that, in the absence of plasma cells, inflammatory symptoms of an MS-like disease state in a mouse model were more severe. Additionally, IgA-producing plasma cells were directly responsible for suppressing neuroinflammation.

To see if these results extended to human MS patients, they also tested the IgA content within the gut — the region of the body containing the largest reservoir of IgA-producing cells. They saw that relapsing MS patients had significantly less IgA gut bacteria than patients who were in remission. This indicated a potential migration of IgA cells out of the gut, precipitating the inflammatory relapse in MS.

The results of the study suggest not only that gut-derived IgA plasma cells can access the inflamed CNS in MS, but also that they play an important role in regulating the tissue inflammatory response. This demonstrates the necessity of considering the gut-brain axis when treating the pathology of inflammatory disease, as well as the therapeutic potential of mobilizing immunosuppressive IgA-producing cells from the gut to the CNS.

In the future, Gommerman plans to further examine which microbes in the gut promote the accumulation of resident reactive IgA plasma cells in the CNS. With her team, she hopes to design therapies that will promote the accumulation of these cells in nervous tissue.

“The problem with treating MS is that it is hard to get therapies into the CNS,” said Gommerman. “However, IgA plasma cells migrate to the CNS on their own. Thus, mobilizing these cells to enter the CNS may represent a novel strategy for quieting inflammation in the CNS.”