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Aryl hydrocarbon receptor control of a disease tolerance defence pathway

Author

Listed:
  • Alban Bessede

    (University of Perugia, 06132 Perugia, Italy
    IMS Laboratory, University of Bordeaux, 33607 Pessac, France)

  • Marco Gargaro

    (University of Perugia, 06132 Perugia, Italy)

  • Maria T. Pallotta

    (University of Perugia, 06132 Perugia, Italy)

  • Davide Matino

    (University of Perugia, 06132 Perugia, Italy)

  • Giuseppe Servillo

    (University of Perugia, 06132 Perugia, Italy)

  • Cinzia Brunacci

    (University of Perugia, 06132 Perugia, Italy)

  • Silvio Bicciato

    (Center for Genome Research, University of Modena and Reggio Emilia, 41125 Modena, Italy)

  • Emilia M. C. Mazza

    (Center for Genome Research, University of Modena and Reggio Emilia, 41125 Modena, Italy)

  • Antonio Macchiarulo

    (University of Perugia, 06123 Perugia, Italy)

  • Carmine Vacca

    (University of Perugia, 06132 Perugia, Italy)

  • Rossana Iannitti

    (University of Perugia, 06132 Perugia, Italy)

  • Luciana Tissi

    (University of Perugia, 06132 Perugia, Italy)

  • Claudia Volpi

    (University of Perugia, 06132 Perugia, Italy)

  • Maria L. Belladonna

    (University of Perugia, 06132 Perugia, Italy)

  • Ciriana Orabona

    (University of Perugia, 06132 Perugia, Italy)

  • Roberta Bianchi

    (University of Perugia, 06132 Perugia, Italy)

  • Tobias V. Lanz

    (Experimental Neuroimmunology Unit, German Cancer Research Center, 69120 Heidelberg, Germany
    University Hospital, 69120 Heidelberg, Germany)

  • Michael Platten

    (Experimental Neuroimmunology Unit, German Cancer Research Center, 69120 Heidelberg, Germany
    University Hospital, 69120 Heidelberg, Germany)

  • Maria A. Della Fazia

    (University of Perugia, 06132 Perugia, Italy)

  • Danilo Piobbico

    (University of Perugia, 06132 Perugia, Italy)

  • Teresa Zelante

    (University of Perugia, 06132 Perugia, Italy)

  • Hiroshi Funakoshi

    (Center for Advanced Research and Education, Asahikawa Medical University, 078-8510 Asahikawa, Japan)

  • Toshikazu Nakamura

    (Center for Advanced Science and Innovation, Osaka University, 565-0871 Osaka, Japan)

  • David Gilot

    (CNRS UMR6290, Institut de Génétique et Développement de Rennes, Université de Rennes 1, 35043 Rennes, France)

  • Michael S. Denison

    (University of California)

  • Gilles J. Guillemin

    (Australian School of Advanced Medicine (ASAM), Macquarie University, 2109 New South Wales, Australia)

  • James B. DuHadaway

    (Lankenau Institute for Medical Research)

  • George C. Prendergast

    (Lankenau Institute for Medical Research)

  • Richard Metz

    (New Link Genetics Corporation)

  • Michel Geffard

    (IMS Laboratory, University of Bordeaux, 33607 Pessac, France)

  • Louis Boon

    (Bioceros, 3584 Utrecht, The Netherlands)

  • Matteo Pirro

    (University of Perugia, 06132 Perugia, Italy)

  • Alfonso Iorio

    (McMaster University, Ontario L8S 4K1, Canada)

  • Bernard Veyret

    (IMS Laboratory, University of Bordeaux, 33607 Pessac, France)

  • Luigina Romani

    (University of Perugia, 06132 Perugia, Italy)

  • Ursula Grohmann

    (University of Perugia, 06132 Perugia, Italy)

  • Francesca Fallarino

    (University of Perugia, 06132 Perugia, Italy)

  • Paolo Puccetti

    (University of Perugia, 06132 Perugia, Italy)

Abstract

Disease tolerance is the ability of the host to reduce the effect of infection on host fitness. Analysis of disease tolerance pathways could provide new approaches for treating infections and other inflammatory diseases. Typically, an initial exposure to bacterial lipopolysaccharide (LPS) induces a state of refractoriness to further LPS challenge (endotoxin tolerance). We found that a first exposure of mice to LPS activated the ligand-operated transcription factor aryl hydrocarbon receptor (AhR) and the hepatic enzyme tryptophan 2,3-dioxygenase, which provided an activating ligand to the former, to downregulate early inflammatory gene expression. However, on LPS rechallenge, AhR engaged in long-term regulation of systemic inflammation only in the presence of indoleamine 2,3-dioxygenase 1 (IDO1). AhR-complex-associated Src kinase activity promoted IDO1 phosphorylation and signalling ability. The resulting endotoxin-tolerant state was found to protect mice against immunopathology in Gram-negative and Gram-positive infections, pointing to a role for AhR in contributing to host fitness.

Suggested Citation

  • Alban Bessede & Marco Gargaro & Maria T. Pallotta & Davide Matino & Giuseppe Servillo & Cinzia Brunacci & Silvio Bicciato & Emilia M. C. Mazza & Antonio Macchiarulo & Carmine Vacca & Rossana Iannitti , 2014. "Aryl hydrocarbon receptor control of a disease tolerance defence pathway," Nature, Nature, vol. 511(7508), pages 184-190, July.
    • Handle: RePEc:nat:nature:v:511:y:2014:i:7508:d:10.1038_nature13323
    DOI: 10.1038/nature13323
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    Cited by:

    1. Luis Ricardo Linard Martins & Kinga Grzech-Leśniak & Nidia Castro dos Santos & Lina J. Suárez & Gabriela Giro & Marta Ferreira Bastos & Jamil Awad Shibli, 2022. "Transcription Factor AhR, Cytokines IL-6 and IL-22 in Subjects with and without Peri-Implantitis: A Case Control-Study," IJERPH, MDPI, vol. 19(12), pages 1-10, June.
    2. Dongni Shi & Xianqiu Wu & Yunting Jian & Junye Wang & Chengmei Huang & Shuang Mo & Yue Li & Fengtian Li & Chao Zhang & Dongsheng Zhang & Huizhong Zhang & Huilin Huang & Xin Chen & Y. Alan Wang & Chuyo, 2022. "USP14 promotes tryptophan metabolism and immune suppression by stabilizing IDO1 in colorectal cancer," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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