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Summary
Taste receptors, initially identified in the oral epithelium, have since been shown to be widely distributed, being found in the upper and lower respiratory tracts, gastrointestinal epithelium, thyroid, and brain. The presence of taste receptors in the nasal epithelium has led to the discovery of their role in innate immunity, defending the paranasal sinuses against pathogens. This article addresses the current paradigm for understanding the role of extraoral taste receptors, specifically the T2R38 bitter taste receptor and the T1R2+3 sweet taste receptor, in respiratory innate defenses and presents evidence for the use of these and other taste receptors as therapeutic targets in the management of chronic rhinosinusitis. Future studies should focus on understanding the polymorphisms of taste receptors beyond T2R38 to fully elucidate their potential therapeutic use and lay the groundwork for their modulation in a clinical setting to decrease the health impact and economic burden of upper respiratory disease.
Financial & competing interests disclosure
Some of the research described here was supported by R01DC013588 to NA Cohen and by R21DC013886 to NA Cohen and DR Reed. We acknowledge the technical assistance of Charles J. Arayata and the editorial assistance of Patricia J. Watson. NA Cohen and DR Reed are co-inventors on a patent under review (Therapy and Diagnostics for Respiratory Infection 61/697,652, WO2013112865). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Chronic rhinosinusitis (CRS) represents a spectrum of chronic disease with significant morbidity and causes a greater decrease in quality of life than does chronic obstructive pulmonary disease, congestive heart failure, or angina.
The T2R38 bitter taste receptor exists primarily in one of two polymorphisms: the active (PAV) form senses bitter compounds and exhibits antimicrobial response in the nasal epithelium, and the inactive (AVI) form does not. The response of individuals heterozygous for the receptor (AVI/PAV) is variable.
The majority of bitter taste receptors contain common polymorphisms with possible innate immune functional consequences.
The role of extraoral taste receptors has been suggested in the pathogenesis of CRS, with studies linking T2R38 genotype and susceptibility to sinonasal infections, and CRS requiring surgical management.
Two primary cell types contribute to extraoral taste-receptor-mediated antimicrobial responses: (1) nasal solitary chemosensory cells (SCCs) express taste receptors. Stimulation of the SCC bitter receptor(s) induces secretion of antimicrobial peptides, while stimulation of sweet receptor T1R2 + 3 blocks the T2R antimicrobial peptide release. (2) Ciliated epithelial cells express T2R38, whose stimulation induces nitric oxide production, with direct bactericidal activity, and simultaneous increase in ciliary beat frequency and mucociliary clearance.
Stimulation of the T2R38 and antagonism of the T1R2 + 3 sweet taste receptors represents a putative therapeutic target in the management of CRS.
Taste receptor pharmacotherapy represents an alternative to local alpha agonist therapy with a mechanism of action that bypasses the tachyphylaxis and rhinitis medicamentosa plaguing current therapeutics.
SCCs may contribute to the pathophysiology of nonallergic, vasomotor rhinitis. This may secondarily create a limitation to their therapeutic use in the T2R-dependent modulation of upper airway disease.
Stratification of patients by T2R38 genotype could become the standard of care in managing patients with refractory CRS.