The bitter taste receptor TAS2R38 may play a role in innate defense, say researchers, who have found that variations in the TAS2R38 gene may regulate susceptibility to respiratory infection.
Robert Lee (University of Pennsylvania, Philadelphia, USA) and co-authors used immunofluorescent and live cell imaging techniques in polarized primary human sinonasal cells to demonstrate that TAS2R38, the receptor for the compound phenylthiocarbamide (PTC), is expressed in human upper respiratory epithelium.
They also found that TAS2R38 is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Activation of the receptor regulates calcium-dependent nitric oxide (NO) production, which results in stimulation of mucociliary clearance - the primary defense of the respiratory system - and direct antibacterial effects, Lee and team say.
Moreover, the team observed that common polymorphisms of the TAS2R38 gene were associated with significant differences in the ability of upper respiratory cells to clear and kill bacteria.
"Upper airway epithelial cells from individuals with one or two nonfunctional TAS2R38 alleles [AVI/PAV or PAV/AVI] have significantly blunted NO and ciliary responses following exposure to gram-negative quorum-sensing molecules, and these individuals are more likely to be infected with gram-negative bacteria such as P. aeruginosa than those with two functional receptor alleles [PAV/PAV] ," explain the authors.
Lee et al believe that their data provide preclinical evidence to instigate a clinical trial to prospectively define the clinical course of patients with various TAS2R38 genotypes while simultaneously phenotyping their response to a bitter taste test.
"If gustatory response to PTC accurately predicts rates of sinonasal infection or response to therapy for a sinonasal infection, a bitter taste test could serve as an indicator for aggressive therapy in rhinosinusitis," they explain in the Journal of Clinical Investigation.
Lee and team add: "Since even individuals with nonfunctional alleles will respond to high concentrations of TAS2R38 agonists, topical application of such agonists may have therapeutic potential for multiple forms of upper respiratory infections."
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