Document Detail


T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection.
MedLine Citation:
PMID:  23041624     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Robert J Lee; Guoxiang Xiong; Jennifer M Kofonow; Bei Chen; Anna Lysenko; Peihua Jiang; Valsamma Abraham; Laurel Doghramji; Nithin D Adappa; James N Palmer; David W Kennedy; Gary K Beauchamp; Paschalis-Thomas Doulias; Harry Ischiropoulos; James L Kreindler; Danielle R Reed; Noam A Cohen
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-01     Completed Date:  2013-01-15     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4145-59     Citation Subset:  AIM; IM    
Affiliation:
Department of Otorhinolaryngology, Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Female
Genetic Predisposition to Disease*
Humans
Immunity, Innate / genetics
Male
Nasal Mucosa* / immunology,  metabolism,  microbiology
Paranasal Sinuses* / immunology,  metabolism,  microbiology
Polymorphism, Genetic*
Pseudomonas Infections* / genetics,  immunology,  metabolism
Pseudomonas aeruginosa* / immunology,  metabolism
Quorum Sensing / immunology
Receptors, G-Protein-Coupled* / genetics,  immunology,  metabolism
Rhinitis* / genetics,  immunology,  metabolism,  microbiology
Grant Support
ID/Acronym/Agency:
P30 DC011735/DC/NIDCD NIH HHS; P30DC011735/DC/NIDCD NIH HHS; P50DC000214/DC/NIDCD NIH HHS; R01 DC004698/DC/NIDCD NIH HHS; R01 DC010842/DC/NIDCD NIH HHS; R01DC004698/DC/NIDCD NIH HHS; R01DC010842/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, G-Protein-Coupled; 0/taste receptors, type 2
Comments/Corrections
Comment In:
J Clin Invest. 2012 Nov 1;122(11):3847-9   [PMID:  23041625 ]
Nat Rev Immunol. 2012 Nov;12(11):746   [PMID:  23080389 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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