Histamine receptor 2 modifies dendritic cell responses to microbial ligands - 27/06/13
Abstract |
Background |
The induction of tolerance and protective immunity to microbes is significantly influenced by host- and microbiota-derived metabolites, such as histamine.
Objective |
We sought to identify the molecular mechanisms for histamine-mediated modulation of pattern recognition receptor signaling.
Methods |
Human monocyte-derived dendritic cells (MDDCs), myeloid dendritic cells, and plasmacytoid dendritic cells were examined. Cytokine secretion, gene expression, and transcription factor activation were measured after stimulation with microbial ligands and histamine. Histamine receptor 2 (H2R)–deficient mice, histamine receptors, and their signaling pathways were investigated.
Results |
Histamine suppressed MDDC chemokine and proinflammatory cytokine secretion, nuclear factor κB and activator protein 1 activation, mitogen-activated protein kinase phosphorylation, and TH1 polarization of naive lymphocytes, whereas IL-10 secretion was enhanced in response to LPS and Pam3Cys. Histamine also suppressed LPS-induced myeloid dendritic cell TNF-α secretion and suppressed CpG-induced plasmacytoid dendritic cell IFN-α gene expression. H2R signaling through cyclic AMP and exchange protein directly activated by cyclic AMP was required for the histamine effect on LPS-induced MDDC responses. Lactobacillus rhamnosus, which secretes histamine, significantly suppressed Peyer patch IL-2, IL-4, IL-5, IL-12, TNF-α, and GM-CSF secretion in wild-type but not H2R-deficient animals.
Conclusion |
Both host- and microbiota-derived histamine significantly alter the innate immune response to microbes through H2R.
Le texte complet de cet article est disponible en PDF.Key words : Dendritic cell, microbiota, pattern recognition receptors, histamine, histamine receptors, nuclear factor κB, cyclic AMP, Lactobacillus rhamnosus
Abbreviations used : AP-1, cAMP, DC, Epac, Foxp3, H1R, H2R, H4R, mDC, MDDC, NF-κB, pDC, PKA, PMA, PRR, TLR
Plan
| Supported by Swiss National Foundation grants (project nos. 310030-127356 and 32003027618/1), the Christine Kühne-Center for Allergy Research and Education (CK-CARE), European Union research grants, COST Action BM0806, and European Union Marie Curie grants. |
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| Disclosure of potential conflict of interest: T. Watanabe has received grants and travel support from MEXT. R. Lauener has received grants from the Kühne Foundation and the European Union and serves on advisory boards of Merck Sharp & Dohme, Novartis, Nestlé, and Menarini. C. A. Akdis has consultant arrangements with Actellion, Aventis, Stallergenes, Allergopharma, and Circacia; is employed by the Swiss Institute of Allergy and Asthma Research; and has received grants from Novartis, PREDICTA: European Commission's Seventh Framework, the Swiss National Science Foundation, MeDALL: European Commission's Seventh Framework Programme, and the Christine Kühne-Center for Allergy Research and Education. L. O'Mahony has received grants from the Swiss National Science Foundation and the European Union and has consultant arrangements with Alimentary Health Ltd. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 132 - N° 1
P. 194 - juillet 2013 Retour au numéro
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