The role of taste receptor cells in periodontal homeostasis

Periodontal disease, caused by bacterial infection and inflammation of the gums and supporting bone, affects nearly 50% of U.S. adults over the age of 30, with approximately 9% suffering from severe periodontitis. The hallmark of this disease is the progressive destruction of alveolar bone, ultimately leading to tooth loss and significant oral disability. Periodontitis is particularly prevalent among older adults and is associated with increased risk for systemic conditions such as atherosclerosis, rheumatoid arthritis, and diabetes mellitus. The disease arises from polymicrobial dysbiosis that disrupts the balanced oral microbiota, alongside impaired host innate immune responses that contribute to tissue destruction. While the roles of microbial communities and immune dysfunction in periodontitis are well established, the specific gingival cell types involved in protective responses remain poorly understood. Recent studies have identified taste-like chemosensory cells—solitary chemosensory cells (SCCs) and tuft cells—in various mucosal tissues as key sentinels that detect microbial signals and initiate innate immune responses. Building on this, our preliminary work has identified SCCs and macrophages (MΦ) in the mouse gingiva as components of the epithelial barrier that protect against bacterial invasion. Both cell types express bitter taste receptors and associated signaling components, respond to bitter and bacterial stimuli, and activate innate immune pathways that mitigate periodontal inflammation and bone loss. This proposal aims to expand upon these findings by: • Aim 1: Investigating how taste signaling in gingival macrophages contributes to both the pathogenesis and protection mechanisms in periodontal disease. • Aim 2: Identifying the protective mechanisms by which gingival SCCs and MΦ reduce periodontal bone loss in response to bitter compound stimulation. Overall, this study represents a significant advancement in our understanding of periodontal disease pathophysiology. Activating SCCs and MΦ through bitter compounds offers a novel, non-invasive therapeutic strategy. Furthermore, this approach holds promise for clinical translation through advanced delivery systems such as nanoparticles and hydrogels. Project Number: 1R01DE035102-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: Marco Tizzano | Institution: UNIVERSITY OF PENNSYLVANIA, PHILADELPHIA, PA | Award Amount: $522,405 | Activity Code: R01 | Study Section: Oral, Dental and Craniofacial Sciences Study Section[ODCS] View on NIH RePORTER: https://reporter.nih.gov/project-details/11367193