Abstract
Burn injury causes an immunosuppression associated with suppressed adaptive immune function. Dendritic cells (DCs) are APCs for which signaling via their Toll-like receptors (TLRs) induces their maturation and activation, which is essential for the adaptive immune response. In this study, we examined if burn injury alters the TLR activity of splenic DCs. After injury, we noticed that DC functions were impaired, characterized by a suppressed capacity to prime naive T cells when triggering the TLR4 signaling cascade using specific ligands (LPS or rHSP60). The observed perturbations on LPS-primed DCs isolated from burned mice exhibited significantly diminished IL-12p40 production and enhanced IL-10 secretion-associated impairment in mitogen-activated protein kinase activation. Interestingly, we observed a decrease of TLR4/MD-2 expression on the CD8α+ DC subset that persisted following LPS stimulation. The altered TLR4 expression on LPS-stimulated CD8α+ DCs was associated with reduced capacity to produce IL-12 after stimulation. Our results suggested that TLR4 reactivity on DCs, especially CD8α+ DCs, is disturbed after burn injury.
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Acknowledgments
This work was supported by a grant from the Fondation des Pompiers du Québec pour les Grands-Brûlés. Michele D'Elia and Julie Patenaude were supported by a research award from the FRSQ-Fondation de la Recherche en Santé du Québec.
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Patenaude, J., D’Elia, M., Hamelin, C. et al. Selective effect of burn injury on splenic CD11c+ dendritic cells and CD8α+CD4−CD11c+ dendritic cell subsets. Cell. Mol. Life Sci. 67, 1315–1329 (2010). https://doi.org/10.1007/s00018-009-0251-8
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DOI: https://doi.org/10.1007/s00018-009-0251-8