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Dendritic cell quiescence during systemic inflammation driven by LPS stimulation of radioresistant cells in vivo


Nolte, Martijn A; LeibundGut-Landmann, Salomé; Joffre, Olivier; Sousa, Caetano Reis e (2007). Dendritic cell quiescence during systemic inflammation driven by LPS stimulation of radioresistant cells in vivo. Journal of Experimental Medicine, 204(6):1487-1501.

Abstract

Dendritic cell (DC) activation is a prerequisite for T cell priming. During infection, activation can ensue from signaling via pattern-recognition receptors after contact with pathogens or infected cells. Alternatively, it has been proposed that DCs can be activated indirectly by signals produced by infected tissues. To address the contribution of tissue-derived signals, we measured DC activation in a model in which radioresistant cells can or cannot respond to lipopolysaccharide (LPS). We report that recognition of LPS by the radioresistant compartment is sufficient to induce local and systemic inflammation characterized by high circulating levels of tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, IL-6, and CC chemokine ligand 2. However, this is not sufficient to activate DCs, whether measured by migration, gene expression, phenotypic, or functional criteria, or to render DC refractory to subsequent stimulation with CpG-containing DNA. Similarly, acute or chronic exposure to proinflammatory cytokines such as TNF-alpha +/- interferon alpha/beta has marginal effects on DC phenotype in vivo when compared with LPS. In addition, DC activation and migration induced by LPS is unimpaired when radioresistant cells cannot respond to the stimulus. Thus, inflammatory mediators originating from nonhematopoietic tissues and from radioresistant hematopoietic cells are neither sufficient nor required for DC activation in vivo.

Abstract

Dendritic cell (DC) activation is a prerequisite for T cell priming. During infection, activation can ensue from signaling via pattern-recognition receptors after contact with pathogens or infected cells. Alternatively, it has been proposed that DCs can be activated indirectly by signals produced by infected tissues. To address the contribution of tissue-derived signals, we measured DC activation in a model in which radioresistant cells can or cannot respond to lipopolysaccharide (LPS). We report that recognition of LPS by the radioresistant compartment is sufficient to induce local and systemic inflammation characterized by high circulating levels of tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, IL-6, and CC chemokine ligand 2. However, this is not sufficient to activate DCs, whether measured by migration, gene expression, phenotypic, or functional criteria, or to render DC refractory to subsequent stimulation with CpG-containing DNA. Similarly, acute or chronic exposure to proinflammatory cytokines such as TNF-alpha +/- interferon alpha/beta has marginal effects on DC phenotype in vivo when compared with LPS. In addition, DC activation and migration induced by LPS is unimpaired when radioresistant cells cannot respond to the stimulus. Thus, inflammatory mediators originating from nonhematopoietic tissues and from radioresistant hematopoietic cells are neither sufficient nor required for DC activation in vivo.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Virology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:11 June 2007
Deposited On:04 Jul 2019 11:37
Last Modified:31 Jul 2020 03:27
Publisher:Rockefeller University Press
ISSN:0022-1007
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1084/jem.20070325
PubMed ID:17548522

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