Pedro Moura-Alves, Max Planck Institute for Infection Biology, Berlin, Germany
The aryl hydrocarbon receptor (AhR) is a highly conserved ligand-dependent transcription factor that was initially studied in the context of detoxification. In the last years the role of AhR in several biological processes has been shown, expanding from xenobiotic metabolism to cell cycle regulation, hormone regulation and immune responses, amongst others. Recently we have found that AhR is involved in sensing bacterial pigments, namely the phenazines from Pseudomonas aeruginosa and the naphtoquine phthiocol from Mycobacterium tuberculosis.
Upon ligand binding, AhR activation leads to virulence factor degradation and regulated cytokine and chemokine production, in both epithelial and myeloid cells. The relevance of AhR to host defense is underlined by heightened susceptibility of AhR-deficient mice to both infections. Currently we are expanding our knowledge on the role of AhR in the modulation of innate immune responses during the course of P. aeruginosa infection. Taking advantage of a zebrafish model, we were capable of demonstrating direct AhR activation upon recognition of bacterial ligands in vivo. Moreover, we have identified several other ligands, expressed at different stages of infection, capable of modulating the immune responses via AhR, both in vitro and in vivo. Our results point to a dynamic process regulating the immune responses during the course of P. aeruginosa infection, where AhR is one of the major host players.
Moura-Alves P et al. (2014) AhR sensing of bacterial pigments regulates antibacterial defense Nature 512:387-92.
Contact: Olivier Neyrolles
11:00 - 12:00
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