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Histamine receptor 2 modifies dendritic cell responses to microbial ligands


Frei, Remo; Ferstl, Ruth; Konieczna, Patrycja; Ziegler, Mario; Simon, Tunde; Rugeles, Tulia Mateus; Mailand, Susanne; Watanabe, Takeshi; Lauener, Roger; Akdis, Cezmi A; O'Mahony, Liam (2013). Histamine receptor 2 modifies dendritic cell responses to microbial ligands. Journal of Allergy and Clinical Immunology, 132(1):194-204.

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 T(H)1 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.

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 T(H)1 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.

Citations

21 citations in Web of Science®
24 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:05 Feb 2014 15:30
Last Modified:05 Apr 2016 17:30
Publisher:Elsevier
ISSN:0091-6749
Publisher DOI:https://doi.org/10.1016/j.jaci.2013.01.013
PubMed ID:23465664

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