Chewing Your Food Boosts Immune Response Against Illness

The food we eat provides a wealth of nutrients for our immune system which is constantly fighting against invaders on our behalf to keep us healthy. Researchers from the University of Manchester and the National Institutes of Health in the United States have recently found that chewing your food also plays a role in how your ability to fight off infections.

When it comes to that immunity response, T helper 17 (Th17) immune cells are active players in fighting off infections typically associated with the mouth, according to a recent press release on the study, published in the journal, Immunity. In their research, the authors made a number of discoveries regarding these important cells, chief among them was the fact that these cells are a central part of the mouth’s defense.

“The immune system performs a remarkable balancing act at barrier sites such as the skin, mouth, and gut by fighting off harmful pathogens while tolerating the presence of normal friendly bacteria,” said, lead researcher Joanne Konkel, PhD, biologist from The University of Manchester in the press release.

Dr. Konkel and her team defined these cells as the “key mediators of barrier immunity participating in immune surveillance and maintenance of barrier integrity,” in the study. Furthermore, this specific subset of T cells is known to act as mediators when it comes to protective immunity and “pathogenic inflammation at the oral barrier.”

The Amount of Th17 Cells Increase with Age

Further exploration of Th17 cells yielded a wealth of insight. First, the researchers found that the amount of Th17 cells in the gingiva, or gums, actually increase with age. By examining the IL-17+ T cells in the gingiva of mice, the researchers found that the older the mice were, the more T cells there were. “Few Th17 cells were seen in the gingiva of 8-week-old (young) mice. However, by 24 weeks of age, considered middle age in aging studies, Th17 cell frequencies and numbers were significantly elevated in the gingiva, indicating the physiologic development of a Th17 cell network with age.”

The researchers extended their study to examine IL-17+ cell frequencies in human gingiva as well. Examining these frequencies in both younger (18 to 25 years of age) and older (40 to 50 years of age) participants—all healthy, with no evidence of any oral disease—the researchers noted similar findings, stating, “We saw increased frequencies of IL-17+ cells in the gingiva of older compared to younger adults.”

Th17 Cell Development Is Not Dependent on Commensal Bacteria

Unlike at other barrier sites, such as the gastrointestinal tract or the skin, the researchers also found that Th17 cells do not depend on commensal bacteria to develop. By examining the cells in 24-week-old mice, with and without the presence of segmented filamentous bacteria (SFB), they found that the frequencies of the cells did not differ, regardless of whether the bacteria were present or not, thus proving that the Th17 cells develop independent from commensal bacteria.

These findings prompted the researchers to investigate the cytokine cues that are needed in order to develop these cells. Since IL-1 and IL-23 cytokines are key players in the development of Th17 cells in other barriers, such as the gastrointestinal tract and skin, the researchers decided to start looking at these areas first. According to the study, the researchers quickly found that these cytokines were “dispensable for gingival Th17 cells as shown by the fact cytokine-deficient animals, specifically il1a/b^−/− (il1a and il1b double-deficient mice) and il1r1^−/− as well as il23a^−/− and il12b^−/− mice exhibited unchanged frequencies of gingival Th17 cells.” Based on the results of past studies, cited in their paper, the researchers knew that a cytokine called IL-6 actually promotes differentiation in these cells. In this study, they “found that development of gingival Th17 cells was dependent on IL-6 as Th17 cells were drastically reduced in the gingiva of il6-deficient animals.”

Physiological Mechanical Damage Caused by Chewing Promotes Th17 Cell Development

The researchers sought to figure out just how the Th17 cells were able to develop without commensal bacteria. They found that what drives these cells is on-going mastication (chewing), or what they say is a “unique tissue-specific signal.”

In order to understand how mastication affects the role of Th17 cells, the researchers first “reduced the mechanical forces of mastication on the oral barrier” by putting newly-weaned mice on softer diets until they were 24 weeks old. At 24 weeks, they examined the gingiva Th17 cells and found that a “reduction in the physiological stimuli induced by mastication resulted in a significant decrease in gingiva Th17 cells.” This means that with a softer diet, less damage was done to the gingiva, and thus, less Th17 cells were stimulated. Next, in order to “directly assess whether local barrier damage was a stimulus promoting gingival Th17 cells,” the researchers increased gingival damage in young mice that did not have many Th17 cells; they did this by rubbing a sterile cotton applicator to the gingiva every other day over the course of 11 days.

They found that this resulted in “increased frequencies and numbers of gingival Th17 cells.” After changing the hardness of the food, the researchers realized that chewing was a critical factor in the stimulation of Th17 cells because of the changes that they found in Th17 cell frequency after the dietary changes. Knowing this, the researchers hypothesized that the damage caused by mastication actually works to induce the Th17 cells, stimulating a protective response in the oral barrier.

“Our research shows that, unlike any other barriers, the mouth has a different way of stimulating Th17 cells; not by bacteria but by mastication. Therefore, mastication can induce a protective immune response in our gums,” Dr. Konkel explained in the press release.

Too Many Th17 Cells Can Contribute to Periodontitis

Interestingly, the researchers also found that the physiologic damage caused by mastication may in fact generate too many of Th17 cells, which can result in a number of complications. According to the authors, “While mechanical damage-induced Th17 cells could mediate a degree of barrier protection, as Th17 cells are associated with periodontal bone loss we speculated that long-term exposure to these immune mediators could be detrimental and mediate pathogenic consequences at the gingiva.” In fact, after measuring periodontal bone heights and “documented periodontal bone loss” in both 24-week-old and 8-week-old mice, they found that physiological mechanical damage was actually a key driver of bone loss. By feeding weaning mice a soft diet until 24-weeks of age they found that “reduction in mastication-induced damage resulted in significantly less alveolar bone loss compared to mice fed normal chow.”

Although, Th17 cells can serve as protectors of the oral barrier, in excess, they can lead to a number of health issues. When speaking of the implications of these findings, Dr. Konkel said in the press release, “Importantly, because inflammation in the mouth is linked to development of diseases all around the body understanding the tissue-specific factors that regulate immunity at the oral barrier could eventually lead to new ways to treat multiple inflammatory conditions.”