The genetics of the bitter taste receptor T2R38 in upper airway innate immunity and implications for chronic rhinosinusitis

Objective Chronic rhinosinusitis (CRS) refractory to therapeutic intervention may involve a particularly resistant infection known as a bacterial biofilm. Critical to biofilm formation is the microbial process of quorum sensing whereby microbes secrete factors that regulate the expression of microbi...

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Bibliographic Details
Published in:The Laryngoscope 2017-01, Vol.127 (1), p.44-51
Main Author: Cohen, Noam A.
Format: Article
Language:English
Subjects:
Biofilms
Cells, Cultured
Chronic Disease
chronic rhinosinusitis
cilia
Cilia - physiology
Fluorescent Antibody Technique
Genes
Genetics
Genotype
host‐pathogen interactions
Humans
Immunity, Innate
interkingdom signaling
Laryngoscopy
Microscopy, Confocal
Microscopy, Electron, Scanning
Mucociliary Clearance
Polymorphism, Single Nucleotide
Receptors, G-Protein-Coupled - genetics
Respiratory Tract Infections - genetics
Respiratory Tract Infections - immunology
Rhinitis
Rhinitis - genetics
Rhinitis - immunology
Sinusitis
Sinusitis - genetics
Sinusitis - immunology
Studies
T2R38
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Summary:Objective Chronic rhinosinusitis (CRS) refractory to therapeutic intervention may involve a particularly resistant infection known as a bacterial biofilm. Critical to biofilm formation is the microbial process of quorum sensing whereby microbes secrete factors that regulate the expression of microbial genes involved in biofilm formation, persistence, and virulence. Here, we review recent work demonstrating that the bitter taste receptor T2R38, expressed on the apical surface of the sinonasal epithelium, serves a sentinel role in eavesdropping on microbial quorum‐sensing communications and regulates localized innate biocidal defenses. Furthermore, studies investigating whether cilia are necessary for T2R38 expression and function in the upper airway are presented. Methods Primary human sinonasal air–liquid interface cultures were used to elucidate cellular pathways responsive to quorum‐sensing molecules, whereas clinical studies investigated the contribution of T2R38 polymorphisms to recalcitrant chronic rhinosinusitis. Results T2R38 is stimulated by acyl‐homoserine lactones, gram‐negative quorum‐sensing molecules, and subsequently activates nitric oxide‐dependent innate immune responses. The formation of mature cilia is necessary for T2R38 expression and function, and polymorphisms that underlie T2R38 functionality appear to be involved in susceptibility to upper respiratory infection and recalcitrant CRS. Conclusion Taste receptors are emerging as critical components of early‐phase respiratory innate immunity, detecting molecules used by microbes to communicate and stimulating localized host defenses. Genetic polymorphisms are very common within the taste receptors, and recent linkage studies have demonstrated associations of taste receptor genetics with CRS. Lastly, ciliogenesis, which is often impacted in CRS, is critical for the functional expression of T2R38. Level of Evidence N/A. Laryngoscope, 127:44–51, 2017
ISSN:0023-852X
1531-4995
DOI:10.1002/lary.26198