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

AhR sensing of bacterial pigments regulates antibacterial defence

Pedro Moura-Alves  1 , Kellen Faé  1 , Erica Houthuys  1 , Anca Dorhoi  1 , Annika Kreuchwig  2 , Jens Furkert  2 , Nicola Barison  3 , Anne Diehl  2 , Antje Munder  4 , Patricia Constant  5 , Tatsiana Skrahina  6 , Ute Guhlich-Bornhof  6 , Marion Klemm  6 , Anne-Britta Koehler  6 , Silke Bandermann  6 , Christian Goosmann  7 , Hans-Joachim Mollenkopf  8 , Robert Hurwitz  9 , Volker Brinkmann  7 , Simon Fillatreau  10 , Mamadou Daffe  5 , Burkhard Tümmler  4 , Michael Kolbe  3 , Hartmut Oschkinat  2 , Gerd Krause  2 , Stefan H E Kaufmann  6
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AhR sensing of bacterial pigments regulates antibacterial defence

Pedro Moura-Alves et al. Nature. .

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.

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