[HTML][HTML] T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection

RJ Lee, G Xiong, JM Kofonow, B Chen… - The Journal of …, 2012 - Am Soc Clin Investig
RJ Lee, G Xiong, JM Kofonow, B Chen, A Lysenko, P Jiang, V Abraham, L Doghramji…
The Journal of clinical investigation, 2012Am Soc Clin Investig
Innate and adaptive defense mechanisms protect the respiratory system from attack by
microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the
mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live
cell imaging techniques in polarized primary human sinonasal cells, we demonstrate that
T2R38 is expressed in human upper respiratory epithelium and is activated in response to
acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa …
Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live cell imaging techniques in polarized primary human sinonasal cells, we demonstrate that T2R38 is expressed in human upper respiratory epithelium and is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Receptor activation regulates calcium-dependent NO production, resulting in stimulation of mucociliary clearance and direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection.
The Journal of Clinical Investigation