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Nature. 2014 Aug 28;512(7515):387-92. doi: 10.1038/nature13684. Epub 2014 Aug 13.

AhR sensing of bacterial pigments regulates antibacterial defence.

Author information

  • 11] Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany [2].
  • 2Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
  • 3Max Planck Institute for Infection Biology, Structural Systems Biology, Charitéplatz 1, 10117 Berlin, Germany.
  • 4Clinical Research Group, Clinic for Pediatric Pneumology, Allergology and Neonatology, OE 6710, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
  • 5Institute of Pharmacology and Structural Biology (IPBS), CNRS and University of Toulouse (Toulouse III), 205 Route de Narbonne, 31077, Toulouse cedex 04, Toulouse, France.
  • 6Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
  • 7Microscopy Core Facility, Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
  • 8Microarray Core Facility, Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
  • 9Protein Purification Core Facility, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
  • 10German Rheumatism Research Centre Berlin (DRFZ), a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.

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.

PMID:
25119038
[PubMed - indexed for MEDLINE]
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