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Abstract and Introduction
Abstract
Purpose of review Taste receptor family 2 (T2R) bitter taste receptors were originally identified and named on the basis of their role in type 2 taste cells of the tongue, in which they serve to detect the presence of potentially harmful ingested chemicals. In 2009, researchers demonstrated that airway epithelial cells also express T2R receptors, but their role in airway physiology and human disease has only recently begun to be identified.
Recent findings Recent research has demonstrated that at least one airway T2R receptor, taste receptor family 2 isoform 38 protein (T2R38) is activated by secreted bacterial products. Activation of T2R38 in sinonasal epithelial cells stimulates nitric oxide production, increasing ciliary beating and directly killing bacteria. Clinical studies have also found correlations of TAS2R38 genotype with susceptibility to gram-negative upper respiratory infection and established T2R38 as an independent risk factor for chronic rhinosinusitis requiring sinus surgery.
Summary These recent studies identify a role for T2R38 in sinonasal innate immunity and chronic rhinosinusitis. Clinical implications include the potential development of T2R38-directed topical therapies, as well as using taste testing and/or genotyping to predict susceptibility to infection. Further studies are needed to more clearly determine how TAS2R38 genotype affects patient outcomes in chronic rhinosinusitis and other upper airway diseases.
Introduction
The immune system has been called the human sixth sense, because it acts as a sensory system to detect invading pathogens. Supporting this viewpoint, recent evidence suggests that the immune and taste systems utilize some of the same chemosensory receptors, namely bitter taste receptors of the taste receptor family 2 (T2R). T2Rs are G-protein-coupled receptors originally identified in type 2 taste receptor cells of the tongue, but expression of T2Rs is now known to extend to multiple organ systems, including the airway. The need to understand the physiology of extraoral T2Rs is highlighted by the fact that many medicinal compounds are bitter; thus, extraoral T2Rs may mediate important off-target drug effects.
Recent basic science and clinical studies are establishing T2Rs as part of a novel pathogen detection network in the airway. T2Rs are expressed in a variety of airway cell types and regulate multiple innate immune responses in both mice and humans. The focus of this review is on a well studied human T2R isoform, taste receptor family 2 isoform 38 protein (T2R38), which is expressed in motile cilia lining the sinonasal cavity (nose and sinuses). T2R38 has recently been linked with sinonasal innate immunity, upper respiratory infection, and chronic rhinosinusitis (CRS), demonstrating that studying extraoral T2Rs has tremendous potential to reveal novel insights into human disease.
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