Aryl hydrocarbon receptor control of a disease tolerance defence pathway

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; Luciana Tissi; Claudia Volpi; Maria L. Belladonna; Ciriana Orabona; Roberta Bianchi; Tobias V. Lanz; Michael Platten; Maria A. Della Fazia; Danilo Piobbico; Teresa Zelante; Hiroshi Funakoshi; Toshikazu Nakamura; David Gilot; Michael S. Denison; Gilles J. Guillemin; James B. Duhadaway; George C. Prendergast; Richard Metz; Michel Geffard; Louis Boon; Matteo Pirro; Alfonso Iorio; Bernard Veyret; Luigina Romani; Ursula Grohmann; Francesca Fallarino; Paolo Puccetti

doi:10.1038/nature13323

Aryl hydrocarbon receptor control of a disease tolerance defence pathway

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, Luciana Tissi, Claudia Volpi, Maria L. Belladonna, Ciriana Orabona, Roberta Bianchi, Tobias V. Lanz, Michael Platten, Maria A. Della Fazia, Danilo PiobbicoTeresa Zelante, Hiroshi Funakoshi, Toshikazu Nakamura, David Gilot, Michael S. Denison, Gilles J. Guillemin, James B. Duhadaway, George C. Prendergast, Richard Metz, Michel Geffard, Louis Boon, Matteo Pirro, Alfonso Iorio, Bernard Veyret, Luigina Romani, Ursula Grohmann, Francesca Fallarino, Paolo Puccetti^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

561 Citations (Scopus)

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.

Original language	English
Pages (from-to)	184-190
Number of pages	7
Journal	Nature
Volume	511
Issue number	7508
DOIs	https://doi.org/10.1038/nature13323
Publication status	Published - 2014

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Bessede, A., Gargaro, M., Pallotta, M. T., Matino, D., Servillo, G., Brunacci, C., Bicciato, S., Mazza, E. M. C., Macchiarulo, A., Vacca, C., Iannitti, R., Tissi, L., Volpi, C., Belladonna, M. L., Orabona, C., Bianchi, R., Lanz, T. V., Platten, M., Della Fazia, M. A., ... Puccetti, P. (2014). Aryl hydrocarbon receptor control of a disease tolerance defence pathway. Nature, 511(7508), 184-190. https://doi.org/10.1038/nature13323

@article{649ee097da6e423db7cc7332fb66fda4,

title = "Aryl hydrocarbon receptor control of a disease tolerance defence pathway",

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.",

author = "Alban Bessede and Marco Gargaro and Pallotta, {Maria T.} and Davide Matino and Giuseppe Servillo and Cinzia Brunacci and Silvio Bicciato and Mazza, {Emilia M C} and Antonio Macchiarulo and Carmine Vacca and Rossana Iannitti and Luciana Tissi and Claudia Volpi and Belladonna, {Maria L.} and Ciriana Orabona and Roberta Bianchi and Lanz, {Tobias V.} and Michael Platten and {Della Fazia}, {Maria A.} and Danilo Piobbico and Teresa Zelante and Hiroshi Funakoshi and Toshikazu Nakamura and David Gilot and Denison, {Michael S.} and Guillemin, {Gilles J.} and Duhadaway, {James B.} and Prendergast, {George C.} and Richard Metz and Michel Geffard and Louis Boon and Matteo Pirro and Alfonso Iorio and Bernard Veyret and Luigina Romani and Ursula Grohmann and Francesca Fallarino and Paolo Puccetti",

year = "2014",

doi = "10.1038/nature13323",

language = "English",

volume = "511",

pages = "184--190",

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Bessede, A, Gargaro, M, Pallotta, MT, Matino, D, Servillo, G, Brunacci, C, Bicciato, S, Mazza, EMC, Macchiarulo, A, Vacca, C, Iannitti, R, Tissi, L, Volpi, C, Belladonna, ML, Orabona, C, Bianchi, R, Lanz, TV, Platten, M, Della Fazia, MA, Piobbico, D, Zelante, T, Funakoshi, H, Nakamura, T, Gilot, D, Denison, MS, Guillemin, GJ, Duhadaway, JB, Prendergast, GC, Metz, R, Geffard, M, Boon, L, Pirro, M, Iorio, A, Veyret, B, Romani, L, Grohmann, U, Fallarino, F & Puccetti, P 2014, 'Aryl hydrocarbon receptor control of a disease tolerance defence pathway', Nature, vol. 511, no. 7508, pp. 184-190. https://doi.org/10.1038/nature13323

TY - JOUR

T1 - Aryl hydrocarbon receptor control of a disease tolerance defence pathway

AU - Bessede, Alban

AU - Gargaro, Marco

AU - Pallotta, Maria T.

AU - Matino, Davide

AU - Servillo, Giuseppe

AU - Brunacci, Cinzia

AU - Bicciato, Silvio

AU - Mazza, Emilia M C

AU - Macchiarulo, Antonio

AU - Vacca, Carmine

AU - Iannitti, Rossana

AU - Tissi, Luciana

AU - Volpi, Claudia

AU - Belladonna, Maria L.

AU - Orabona, Ciriana

AU - Bianchi, Roberta

AU - Lanz, Tobias V.

AU - Platten, Michael

AU - Della Fazia, Maria A.

AU - Piobbico, Danilo

AU - Zelante, Teresa

AU - Funakoshi, Hiroshi

AU - Nakamura, Toshikazu

AU - Gilot, David

AU - Denison, Michael S.

AU - Guillemin, Gilles J.

AU - Duhadaway, James B.

AU - Prendergast, George C.

AU - Metz, Richard

AU - Geffard, Michel

AU - Boon, Louis

AU - Pirro, Matteo

AU - Iorio, Alfonso

AU - Veyret, Bernard

AU - Romani, Luigina

AU - Grohmann, Ursula

AU - Fallarino, Francesca

AU - Puccetti, Paolo

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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U2 - 10.1038/nature13323

DO - 10.1038/nature13323

M3 - Article

C2 - 24930766

AN - SCOPUS:84904216760

SN - 0028-0836

VL - 511

SP - 184

EP - 190

JO - Nature

JF - Nature

IS - 7508

ER -

Aryl hydrocarbon receptor control of a disease tolerance defence pathway

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