Aryl hydrocarbon receptor control of a disease tolerance defense pathway
By A. Bessède, M. Gargaro, M. T. Pallotta, Davide Matino, G. Servillo, Cinzia Brunacci, S. Bicciato, Emilia M. C. Mazza, A. Macchiarulo, C. Vacca and 28 more. Nature, 2014
628 citations recorded by the source corpus.
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.
Subfields: Biochemistry, Biological Psychiatry, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/3c3d1fcb86eb374899601298b9987498c1d314de
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Citations in the corpus
- Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism (2018, background): “T-cells, which protect mice from hyper-inflammatory responses (Bessede et al., 2014).”
- β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance (2016, neutral): “Other, non-TF regulators of tolerance, such as IRAK3, HIF1A, SOCS3, and IDO1, are all more highly expressed in LPS-Mfs compared to naive-Mfs and BG-Mfs and have previously been associated with endotoxin-induced tolerance (Bessede et al., 2014; Saeed et al., 2014; Shalova et al., 2015).”
- Regulation of the immune response by the aryl hydrocarbon receptor (2018, background): “Based on these observations, AhR is likely to play a dual role during bacterial infections, driving certain anti-bacterial activities while simultaneously enforcing ‘‘disease tolerance’’ to minimize immunopathology to the host (Bessede et al., 2014).”
- NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus (2015, background): “These enzymes are strongly overexpressed in diverse cancers, and the subsequent synthesis of kynurenines may act as potential second messengers in cancer immune tolerance (Stone and Darlington, 2002), possibly through binding to the aryl hydrocarbon receptor (AHR) (Bessede et al., 2014).”