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) α, interleukin (IL) 1β, 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-α ± interferon α/β 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.
Dendritic cell quiescence during systemic inflammation driven by LPS stimulation of radioresistant cells in vivo
Abbreviations used: ARE, AU-rich elements; CCL, CC chemokine ligand; CCR, CC chemokine receptor; CXCL, CXC chemokine ligand; GeoMFI, geometric mean fluorescence intensity; PALS, periarteriolar lymphatic sheath; PAMP, pathogen-associated molecular pattern; PRR, pattern-recognition receptor; SOCS, suppressor of cytokine signaling; TLR, Toll-like receptor.
M.A. Nolte's present address is Dept. of Experimental Immunology, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands.
Martijn A. Nolte, Salomé LeibundGut-Landmann, Olivier Joffre, Caetano Reis e Sousa; Dendritic cell quiescence during systemic inflammation driven by LPS stimulation of radioresistant cells in vivo . J Exp Med 11 June 2007; 204 (6): 1487–1501. doi: https://doi.org/10.1084/jem.20070325
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