Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic rhinosinusitis

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.

FIGURE 1

Mucociliary clearance. Inhaled pathogens are trapped by sticky airway mucus secreted by secretory goblet cells and submucosal exocrine glands (not shown). Coordinated ciliary beating then drives the transport of the debris-laden mucus toward the oropharynx, where it is removed by expectoration or swallowing.

FIGURE 2

T2R38 in sinonasal innate immunity. (a) Immunofluorescence confocal micrograph of the apical section of a fixed human sinonasal tissue explant stained using antibodies directed against β-tubulin IV (β-tubIV, with green fluorescent secondary antibody; top panel), a cilia protein, and T2R38 (with red fluorescent secondary antibody; bottom panel), as described in [12^▪▪]. Scale bar is 20 μm. (b) T2R38-activation by bacterial quorum-sensing molecules stimulates calcium-mediated nitric oxide production, which increases ciliary beat frequency and directly kills bacteria. AHL, acyl-homoserine lactone; Ca²⁺, calcium; CBF, ciliary beat frequency; NO, nitric oxide; NOS, nitric oxide synthase; PKG, protein kinase G.