T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection

J Clin Invest. 2012 Nov;122(11):4145-59. doi: 10.1172/JCI64240. Epub 2012 Oct 8.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Immunity, Innate / genetics
  • Male
  • Nasal Mucosa* / immunology
  • Nasal Mucosa* / metabolism
  • Nasal Mucosa* / microbiology
  • Paranasal Sinuses* / immunology
  • Paranasal Sinuses* / metabolism
  • Paranasal Sinuses* / microbiology
  • Polymorphism, Genetic*
  • Pseudomonas Infections* / genetics
  • Pseudomonas Infections* / immunology
  • Pseudomonas Infections* / metabolism
  • Pseudomonas aeruginosa* / immunology
  • Pseudomonas aeruginosa* / metabolism
  • Quorum Sensing / immunology
  • Receptors, G-Protein-Coupled* / genetics
  • Receptors, G-Protein-Coupled* / immunology
  • Receptors, G-Protein-Coupled* / metabolism
  • Rhinitis* / genetics
  • Rhinitis* / immunology
  • Rhinitis* / metabolism
  • Rhinitis* / microbiology


  • Receptors, G-Protein-Coupled
  • taste receptors, type 2