title: AhR sensing of bacterial pigments regulates antibacterial defence.
abstract: The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that senses environmental toxins and endogenous ligands, thereby inducing detoxifying enzymes and modulating immune cell differentiation and responses. We hypothesized that AhR evolved to sense not only environmental pollutants but also microbial insults. We characterized bacterial pigmented virulence factors, namely the phenazines from Pseudomonas aeruginosa and the naphthoquinone phthiocol from Mycobacterium tuberculosis, as ligands of AhR. Upon ligand binding, AhR activation leads to virulence factor degradation and regulated cytokine and chemokine production. The relevance of AhR to host defence is underlined by heightened susceptibility of AhR-deficient mice to both P. aeruginosa and M. tuberculosis. Thus, we demonstrate that AhR senses distinct bacterial virulence factors and controls antibacterial responses, supporting a previously unidentified role for AhR as an intracellular pattern recognition receptor, and identify bacterial pigments as a new class of pathogen-associated molecular patterns.
authors.affiliation: 1] Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany [2].
authors.forename: Pedro
authors.initials: P
authors.lastname: Moura-Alves
authors.affiliation: 1] Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany [2].
authors.forename: Kellen
authors.initials: K
authors.lastname: Faé
authors.affiliation: 1] Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany [2].
authors.forename: Erica
authors.initials: E
authors.lastname: Houthuys
authors.affiliation: 1] Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany [2].
authors.forename: Anca
authors.initials: A
authors.lastname: Dorhoi
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Kreuchwig
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Furkert
authors.affiliation: Max Planck Institute for Infection Biology, Structural Systems Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Barison
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Diehl
authors.affiliation: Clinical Research Group, Clinic for Pediatric Pneumology, Allergology and Neonatology, OE 6710, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Munder
authors.affiliation: Institute of Pharmacology and Structural Biology (IPBS), CNRS and University of Toulouse (Toulouse III), 205 Route de Narbonne, 31077, Toulouse cedex 04, Toulouse, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Constant
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Skrahina
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Guhlich-Bornhof
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Klemm
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Anne-Britta
authors.initials: AB
authors.lastname: Koehler
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Bandermann
authors.affiliation: Microscopy Core Facility, Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Goosmann
authors.affiliation: Microarray Core Facility, Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Mollenkopf
authors.affiliation: Protein Purification Core Facility, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Hurwitz
authors.affiliation: Microscopy Core Facility, Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkmann
authors.affiliation: German Rheumatism Research Centre Berlin (DRFZ), a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Fillatreau
authors.affiliation: Institute of Pharmacology and Structural Biology (IPBS), CNRS and University of Toulouse (Toulouse III), 205 Route de Narbonne, 31077, Toulouse cedex 04, Toulouse, France.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffe
authors.affiliation: Clinical Research Group, Clinic for Pediatric Pneumology, Allergology and Neonatology, OE 6710, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tümmler
authors.affiliation: Max Planck Institute for Infection Biology, Structural Systems Biology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kolbe
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Oschkinat
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Krause
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D025461:Feedback, Physiological; D006801:Humans; D008024:Ligands; D008262:Macrophage Activation; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D010619:Phenazines / Q000378:metabolism; D010860:Pigments, Biological / Q000737:chemistry / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000378:metabolism; D011710:Pyocyanine / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D037521:Virulence Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D008024:Ligands; D010619:Phenazines; D010860:Pigments, Biological; D011710:Pyocyanine; D018336:Receptors, Aryl Hydrocarbon; D051192:Receptors, Pattern Recognition; D037521:Virulence Factors; C484722:Ahr protein, mouse