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T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2012 Nov; Vol. 122 (11), pp. 4145-59. Date of Electronic Publication: 2012 Oct 08. - Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- Cell Line
Female
Humans
Immunity, Innate genetics
Male
Quorum Sensing immunology
Genetic Predisposition to Disease
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
Receptors, G-Protein-Coupled genetics
Receptors, G-Protein-Coupled immunology
Receptors, G-Protein-Coupled metabolism
Rhinitis genetics
Rhinitis immunology
Rhinitis metabolism
Rhinitis microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 122
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 23041624
- Full Text :
- https://doi.org/10.1172/JCI64240