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T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection
Robert J. Lee, … , Danielle R. Reed, Noam A. Cohen
Robert J. Lee, … , Danielle R. Reed, Noam A. Cohen
Published October 8, 2012
Citation Information: J Clin Invest. 2012;122(11):4145-4159. https://doi.org/10.1172/JCI64240.
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Research Article

T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection

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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.

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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Figure 1

T2R38 is expressed at the apical membrane and cilia of sinonasal airway epithelial cells in both human tissue explants and primary human sinonasal ALI cultures.

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T2R38 is expressed at the apical membrane and cilia of sinonasal airway ...
(A–H) Representative images of β-tubulin (green; a ciliary marker), T2R38 (red), and Hoechst (blue; a nuclear stain) in primary human sinonasal tissue (A–D) and in a human sinonasal ALI culture (E–H). Scale bars: 20 μm. The height of the cross-section is stretched to illustrate the co-localization pattern. D and H show cross-sections of z-projections from 4 other tissue samples (D) and from cultures (H) illustrating the co-localization pattern. (I) 32 regions of ciliated cells were analyzed for red and green fluorescence (left to right: basolateral to apical) over approximately 40 pixels.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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