The Role of Bitter and Sweet Taste Receptors in Upper Airway Immunity

Abstract

Over the past several years, taste receptors have emerged as key players in the regulation of innate immune defenses in the mammalian respiratory tract. Several cell types in the airway, including ciliated epithelial cells, solitary chemosensory cells, and bronchial smooth muscle cells, all display chemoresponsive properties that utilize taste receptors. A variety of bitter products secreted by microbes are detected with resultant downstream inflammation, increased mucous clearance, antimicrobial peptide secretion, and direct bacterial killing. Genetic variation of bitter taste receptors also appears to play a role in the susceptibility to infection in respiratory disease states, including that of chronic rhinosinusitis. Ongoing taste receptor research may yield new therapeutics that harness innate immune defenses in the respiratory tract and may offer alternatives to antibiotic treatment. The present review discusses taste receptor-protective responses and analyzes the role these receptors play in mediating airway immune function.

Keywords: Airway immune function; Bitter taste receptor; Solitary chemosensory cell; Sweet taste receptor; T2R38; Upper airway immunity.

Fig. 1

Function of the solitary chemosensory cell (SCC) in innate immune defense in humans. The presence of infectious bacteria decreases glucose concentration in the airway surface liquid (ASL), decreasing stimulation of the T1R receptor and releasing inhibition of T2R signaling. Additionally, the bacteria secrete bitter compounds that directly stimulate the T2R receptors. This propagates a downstream calcium response that spreads to neighboring ciliated cells that secrete antimicrobial peptides that directly kill the inciting pathogen

Fig. 2

T2R38 bitter taste receptor regulation of innate immunity in humans. P. aeruginosa produces acyl-homoserine lactone quorum-sensing molecules, which stimulate the T2R38 bitter taste receptor. This precipitates a downstream calcium response with subsequent nitric oxide (NO) production. The NO diffuses into the airway where it is directly bactericidal and additionally activates protein kinase G to increase ciliary beat frequency and mucociliary clearance