Publication Date:
2014-08-15
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moura-Alves, Pedro -- Fae, Kellen -- Houthuys, Erica -- Dorhoi, Anca -- Kreuchwig, Annika -- Furkert, Jens -- Barison, Nicola -- Diehl, Anne -- Munder, Antje -- Constant, Patricia -- Skrahina, Tatsiana -- Guhlich-Bornhof, Ute -- Klemm, Marion -- Koehler, Anne-Britta -- Bandermann, Silke -- Goosmann, Christian -- Mollenkopf, Hans-Joachim -- Hurwitz, Robert -- Brinkmann, Volker -- Fillatreau, Simon -- Daffe, Mamadou -- Tummler, Burkhard -- Kolbe, Michael -- Oschkinat, Hartmut -- Krause, Gerd -- Kaufmann, Stefan H E -- England -- Nature. 2014 Aug 28;512(7515):387-92. doi: 10.1038/nature13684. Epub 2014 Aug 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Max Planck Institute for Infection Biology, Department of Immunology, Chariteplatz 1, 10117 Berlin, Germany [2]. ; Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rossle-Strasse 10, 13125 Berlin, Germany. ; Max Planck Institute for Infection Biology, Structural Systems Biology, Chariteplatz 1, 10117 Berlin, Germany. ; Clinical Research Group, Clinic for Pediatric Pneumology, Allergology and Neonatology, OE 6710, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. ; Institute of Pharmacology and Structural Biology (IPBS), CNRS and University of Toulouse (Toulouse III), 205 Route de Narbonne, 31077, Toulouse cedex 04, Toulouse, France. ; Max Planck Institute for Infection Biology, Department of Immunology, Chariteplatz 1, 10117 Berlin, Germany. ; Microscopy Core Facility, Max Planck Institute for Infection Biology, Department of Immunology, Chariteplatz 1, 10117 Berlin, Germany. ; Microarray Core Facility, Max Planck Institute for Infection Biology, Department of Immunology, Chariteplatz 1, 10117 Berlin, Germany. ; Protein Purification Core Facility, Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany. ; German Rheumatism Research Centre Berlin (DRFZ), a Leibniz Institute, Chariteplatz 1, 10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25119038" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Anti-Bacterial Agents/metabolism
;
Basic Helix-Loop-Helix Transcription Factors/*metabolism
;
Bone Marrow Cells/cytology
;
Cytokines/immunology/metabolism
;
Feedback, Physiological
;
Humans
;
Ligands
;
Macrophage Activation
;
Mice
;
Mycobacterium tuberculosis/growth & development/*immunology/metabolism
;
Phenazines/metabolism
;
Pigments, Biological/chemistry/*metabolism
;
Pseudomonas Infections/metabolism
;
Pseudomonas aeruginosa/*immunology/metabolism
;
Pyocyanine/metabolism
;
Receptors, Aryl Hydrocarbon/*metabolism
;
Receptors, Pattern Recognition/*metabolism
;
Virulence Factors/chemistry/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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