title: T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection.
abstract: Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live cell imaging techniques in polarized primary human sinonasal cells, we demonstrate that T2R38 is expressed in human upper respiratory epithelium and is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Receptor activation regulates calcium-dependent NO production, resulting in stimulation of mucociliary clearance and direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xiong
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kofonow
authors.forename: Bei
authors.initials: B
authors.lastname: Chen
authors.forename: Anna
authors.initials: A
authors.lastname: Lysenko
authors.forename: Peihua
authors.initials: P
authors.lastname: Jiang
authors.forename: Valsamma
authors.initials: V
authors.lastname: Abraham
authors.forename: Laurel
authors.initials: L
authors.lastname: Doghramji
authors.forename: Nithin D
authors.initials: ND
authors.lastname: Adappa
authors.forename: James N
authors.initials: JN
authors.lastname: Palmer
authors.forename: David W
authors.initials: DW
authors.lastname: Kennedy
authors.forename: Gary K
authors.initials: GK
authors.lastname: Beauchamp
authors.forename: Paschalis-Thomas
authors.initials: PT
authors.lastname: Doulias
authors.forename: Harry
authors.initials: H
authors.lastname: Ischiropoulos
authors.forename: James L
authors.initials: JL
authors.lastname: Kreindler
authors.forename: Danielle R
authors.initials: DR
authors.lastname: Reed
authors.forename: Noam A
authors.initials: NA
authors.lastname: Cohen
mesh_terms: D002460:Cell Line; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010256:Paranasal Sinuses / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011110:Polymorphism, Genetic; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000378:metabolism; D053038:Quorum Sensing / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012220:Rhinitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D000098706:Taste Receptors, Type 2
chemical_list: D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2