Robert Margolskee, MD, PhD Director and President  Monell Center Adjunct Professor, Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine

Sentinels in the Mouth: Special Sensory Cells in the Gums Protect Against Periodontitis

MedicalResearch.com Interview with:

Robert Margolskee, MD, PhD Director and President  Monell Center Adjunct Professor, Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine

Dr. Margolskee

Robert Margolskee, MD, PhD
Director and President
Monell Center
Adjunct Professor, Department of Systems Pharmacology and Translational Therapeutics
University of Pennsylvania Perelman School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We found chemical-sensing cells in the gums that protect the mouth by standing guard against infections that damage soft tissue and destroy the bone that supports the teeth. With the help of bitter taste receptors that also detect byproducts from harmful bacteria, these special gum cells trigger the immune system to control the amount and type of bacteria in the mouth. This knowledge could one day lead to personalized dental treatments against gum disease.

Periodontitis is a serious gum disorder caused by an imbalance in the bacteria and other microorganisms of the mouth. We hope that our new information can help to combat this sixth-most prevalent infectious disease and most common cause of tooth loss worldwide.

MedicalResearch.com: What should readers take away from your report?

Response: We found that the newly identified cells, called solitary chemosensory cells (SCCs), are present in the gums of mice. SCCs are taste-like chemical detectors that sense irritants and bacteria, and biologists have found them throughout the gut, urinary tract, nasal cavities, and now in the gums. These cells express several types of taste receptors along with a taste signaling protein called gustducin. SCCs may provide a new personalized way to treat gum disease by harnessing a person’s own innate immune system to regulate their oral microbiome.

In previous studies with other tissues, other teams found that activating the bitter taste receptor TAS2R38, which is expressed in human nasal SCCs, stimulates the secretion of antimicrobial peptides (AMPs) that repress the growth of pathogens in the airways. We applied a mouthwash containing the ultra-bitter substance denatonium to the gums of the mice twice a day. This activated gum SCCs to produce antimicrobial molecules, which reduced periodontitis in normal mice, but not in the periodontitis-susceptible animals without gustducin.

After receiving the denatonium, normal mice showed an enhanced release of an AMP called β-defensin, which was produced at more than twice the levels seen in control mice treated only with saline mouthwash. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: Mice without gustducin in their SSCs have a more damaging set of microbes living in their mouths compared to normal mice, implying that the lack of gustducin disconnects the sentinel cells’ molecular signal to other systems. Importantly, differences in the oral bacterial composition of the gustducin-less mice compared to normal mice occurred before any loss of bone in the gums, implying that differences in the oral microbiome could be used as a harbinger of disease.

From this animal study, and unpublished work in humans, we expect to find that gum SCCs in people play a similar role in regulating the make-up of the oral microbiome. We suspect that since genetic differences in taste receptors are commonly detected in people — particularly loss-of-function of the bitter taste receptor TAS2R38 – that the dysfunction of taste-receptor-related innate immune responses could be used for dental chair-side screening for individuals who may be the most susceptible to gum disease. 

MedicalResearch.com: Is there anything else you would like to add?

Response: This work was supported by the National Institute on Deafness and Other Communication Disorders, the National Natural Science Foundation of China, and in part, by funding from an NIDCD Core Grant and the National Science Foundation. Additional support came from institutional funds from the Monell Chemical Senses Center. We are an independent nonprofit basic research institute based in Philadelphia, Pennsylvania that studies the mechanisms and functions of taste and smell to benefit human health and wellbeing. 

Citation:

Xin Zheng, Marco Tizzano, Kevin Redding, Jinzhi He, Xian Peng, Peihua Jiang, Xin Xu, Xuedong Zhou, Robert F. Margolskee. Gingival solitary chemosensory cells are immune sentinels for periodontitis. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-12505-x

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Last Updated on October 22, 2019 by Marie Benz MD FAAD