Selective effect of burn injury on splenic CD11c(+) dendritic cells and CD8alpha(+)CD4(-)CD11c(+) dendritic cell subsets.
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 CD8alpha(+) DC subset that persisted following LPS stimulation. The altered TLR4 expression on LPS-stimulated CD8alpha(+) DCs was associated with reduced capacity to produce IL-12 after stimulation. Our results suggested that TLR4 reactivity on DCs, especially CD8alpha(+) DCs, is disturbed after burn injury.
Patenaude
Julie
J
INRS-Institut Armand-Frappier, Laval, QC, Canada.
D'Elia
Michele
M
Hamelin
Claudine
C
Bernier
Jacques
J
D000818:Animals; D015153:Blotting, Western; D002056:Burns / Q000378:metabolism*; D039521:CD11c Antigen / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D016753:Interleukin-10 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D039521:CD11c Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D020928:Mitogen-Activated Protein Kinases