Taste receptor T1R3 in nasal cilia detectsStaphylococcus aureusD-amino acids to increase apical glucose uptake and enhance innate immunity

Abstract

SUMMARYBitter (T2R) and sweet/umami (T1R) taste receptors serve chemosensory roles throughout the body. In airway cilia, T2Rs detect bacterial metabolites to stimulate bactericidal nitric oxide. T1Rs in solitary chemosensory cells detect glucose in airway surface liquid (ASL) and bacterial D-stereoisomer amino acids to regulate antimicrobial peptides. Using differentiated air-liquid interface cultures of primary nasal cells, we show that the T1R3 receptor is also expressed in human and mouse nasal cell cilia. D-amino acids produced at low mM concentrations byStaphylococcus aureusactivate T1R3 to decrease ASL glucose and increase apical glucose uptake by increasing GLUT2 and GLUT10 expression through a β-arrestin pathway. Our data suggests that T1R3 localized to cilia functions as an immune detector for D-amino acids to reduce ASL glucose and potentially limit bacterial growth. Given that glucose protectedS. aureusagainst bactericidal NO produced during T2R activation, the reduced ASL glucose with T1R3 activation may also sensitize bacteria to other innate defenses.HIGHLIGHTSNasal motile cilia express the T1R3 subunit of the sweet taste receptorS. aureusD-amino acids activate cilia T1R3 to enhance mucosal glucose uptakeReduced airway surface liquid glucose likely reducesS. aureusgrowthReduced airway glucose also sensitizesS. aureusto epithelial NO production