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Bitter and sweet taste receptors regulate human upper respiratory innate immunity
Robert J. Lee, … , Robert F. Margolskee, Noam A. Cohen
Robert J. Lee, … , Robert F. Margolskee, Noam A. Cohen
Published February 17, 2014
Citation Information: J Clin Invest. 2014;124(3):1393-1405. https://doi.org/10.1172/JCI72094.
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Research Article Pulmonology Article has an altmetric score of 236

Bitter and sweet taste receptors regulate human upper respiratory innate immunity

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Abstract

Bitter taste receptors (T2Rs) in the human airway detect harmful compounds, including secreted bacterial products. Here, using human primary sinonasal air-liquid interface cultures and tissue explants, we determined that activation of a subset of airway T2Rs expressed in nasal solitary chemosensory cells activates a calcium wave that propagates through gap junctions to the surrounding respiratory epithelial cells. The T2R-dependent calcium wave stimulated robust secretion of antimicrobial peptides into the mucus that was capable of killing a variety of respiratory pathogens. Furthermore, sweet taste receptor (T1R2/3) activation suppressed T2R-mediated antimicrobial peptide secretion, suggesting that T1R2/3-mediated inhibition of T2Rs prevents full antimicrobial peptide release during times of relative health. In contrast, during acute bacterial infection, T1R2/3 is likely deactivated in response to bacterial consumption of airway surface liquid glucose, alleviating T2R inhibition and resulting in antimicrobial peptide secretion. We found that patients with chronic rhinosinusitis have elevated glucose concentrations in their nasal secretions, and other reports have shown that patients with hyperglycemia likewise have elevated nasal glucose levels. These data suggest that increased glucose in respiratory secretions in pathologic states, such as chronic rhinosinusitis or hyperglycemia, promotes tonic activation of T1R2/3 and suppresses T2R-mediated innate defense. Furthermore, targeting T1R2/3-dependent suppression of T2Rs may have therapeutic potential for upper respiratory tract infections.

Authors

Robert J. Lee, Jennifer M. Kofonow, Philip L. Rosen, Adam P. Siebert, Bei Chen, Laurel Doghramji, Guoxiang Xiong, Nithin D. Adappa, James N. Palmer, David W. Kennedy, James L. Kreindler, Robert F. Margolskee, Noam A. Cohen

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Figure 7

Glucose concentrations are elevated in the nasal secretions of patients with CRS.

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Glucose concentrations are elevated in the nasal secretions of patients ...
(A) Glucose was measured in nasal secretions from patients with CRS and control individuals. Glucose was 0.37 ± 0.06 mM vs. 1.63 ± 0.12 mM in control patients (n = 17) and patients with CRS (n = 32), respectively. A significant difference was observed between patients with CRS with (n = 20) and without (n = 12) polyps (1.4 ± 0.1 mM vs. 2.0 ± 0.2 mM, respectively), but nonetheless both groups had significantly higher glucose than control patients (mean ± SEM). *P < 0.05, **P < 0.01, determined via 1-way ANOVA with Tukey-Kramer post-test. (B) In patients with CRS, there was no correlation between blood and nasal secretion glucose concentrations (n = 32 patients for which nasal and blood glucose values could be obtained). Additionally, none of the patients with CRS used in this study had a prior diagnosis of hyperglycemia, prediabetes, or diabetes. Previous studies have shown that hyperglycemia is correlated with increased nasal secretion glucose (51, 74, 75). However, these data suggest that the patients with CRS in this study exhibited higher nasal glucose levels due to another mechanism. (C) Glucose was measured in ASL from ALI cultures, with no difference observed among the populations (mean ± SEM; n = 1 culture each from 5 control patients and 15 patients with CRS, including 6 with polyps and 9 without polyps). No significant differences were detected by 1-way ANOVA.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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