title: Tasting Pseudomonas aeruginosa Biofilms: Human Neutrophils Express the Bitter Receptor T2R38 as Sensor for the Quorum Sensing Molecule N-(3-Oxododecanoyl)-l-Homoserine Lactone.
abstract: Bacteria communicate with one another via specialized signaling molecules, known as quorum sensing molecules or autoinducers. The Pseudomonas aeruginosa-derived quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone (AHL-12), however, also activates mammalian cells. As shown previously, AHL-12-induced chemotaxis, up-regulated CD11b expression, and enhanced phagocytosis of polymorphonuclear neutrophils. Circumstantial evidence concurred with a receptor for AHL-12, which has been elusive so far. We now investigated the bitter receptor T2R38 as a potential candidate. Although identified as a taste receptor, extragustatory cells express T2R38, for example, epithelial cells in the lung. We now detected T2R38 in peripheral blood neutrophils, monocytes, and lymphocytes. T2R38 is not only found on the cell membrane but also intracellular. In neutrophils, T2R38 was located in vesicles with characteristics of lipid droplets, and super-resolution microscopy showed a co-localization with the lipid droplet membrane. Neutrophils take up AHL-12, and it co-localized with T2R38 as seen by laser scan microscopy. Binding of AHL-12 to T2R28 was confirmed by pull-down assays using biotin-coupled AHL-12 as bait. A commercially available antibody to T2R38 inhibited binding of AHL-12 to neutrophils, and this antibody by itself stimulated neutrophils, similarly to AHL-12. In conclusion, our data provide evidence for expression of functional T2R38 on neutrophils, and are compatible with the notion that T2R38 is the receptor for AHL-12.
authors.affiliation: Institute for Immunology, University of Heidelberg , Heidelberg , Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Maurer
authors.affiliation: Institute for Immunology, University of Heidelberg , Heidelberg , Germany.
authors.forename: Guido H
authors.initials: GH
authors.lastname: Wabnitz
authors.affiliation: Institute for Immunology, University of Heidelberg , Heidelberg , Germany.
authors.forename: Nadine A
authors.initials: NA
authors.lastname: Kahle
authors.affiliation: Institute for Immunology, University of Heidelberg , Heidelberg , Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Stegmaier
authors.affiliation: Institute for Immunology, University of Heidelberg , Heidelberg , Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Prior
authors.affiliation: Institute for Immunology, University of Heidelberg , Heidelberg , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.affiliation: Institute for Immunology, University of Heidelberg , Heidelberg , Germany ; Institute of Pathology, University of Heidelberg , Heidelberg , Germany.
authors.forename: Matthias Martin
authors.initials: MM
authors.lastname: Gaida
authors.affiliation: Institute for Immunology, University of Heidelberg , Heidelberg , Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Samstag
authors.affiliation: Institute for Immunology, University of Heidelberg , Heidelberg , Germany.
authors.forename: Gertrud Maria
authors.initials: GM
authors.lastname: Hänsch
keywords: N-(3-oxododecanoyl)-l-homoserine lactone; Pseudomonas aeruginosa; bitter receptor T2R38; lipid droplets; neutrophils; quorum sensing