DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4.
DiC14-amidine cationic liposomes were recently shown to promote Th1 responses when mixed with allergen. To further define the mode of action of diC14-amidine as potential vaccine adjuvant, we characterized its effects on mouse and human myeloid dendritic cells (DC). First, we observed that, as compared with two other cationic liposomes, only diC14-amidine liposomes induced the production of IL-12p40 and TNF-alpha by mouse bone marrow-derived DC. DiC14-amidine liposomes also activated human DC, as shown by synthesis of IL-12p40 and TNF-alpha, accumulation of IL-6, IFN-beta and CXCL10 mRNA, and up-regulation of membrane expression of CD80 and CD86. DC stimulation by diC14-amidine liposomes was associated with activation of NF-kappaB, ERK1/2, JNK and p38 MAP kinases. Finally, we demonstrated in mouse and human cells that diC14-amidine liposomes use Toll-like receptor 4 to elicit both MyD88-dependent and Toll/IL-1R-containing adaptor inducing interferon IFN-beta (TRIF)-dependent responses.
Tanaka
Tetsuya
T
Laboratoire d'Allergologie Expérimentale, Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires, Charleroi, Belgium.
Legat
Amandine
A
Adam
Emmanuelle
E
Steuve
Jonathan
J
Gatot
Jean-Stéphane
JS
Vandenbranden
Michel
M
Ulianov
Liliana
L
Lonez
Caroline
C
Ruysschaert
Jean-Marie
JM
Muraille
Eric
E
Tuynder
Marcel
M
Goldman
Michel
M
Jacquet
Alain
A
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000578:Amidines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D051218:Lymphocyte Antigen 96 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D000276:Adjuvants, Immunologic; D000578:Amidines; D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D051218:Lymphocyte Antigen 96; D020928:Mitogen-Activated Protein Kinases; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C411728:Ly96 protein, mouse; C507780:Myd88 protein, mouse; C089665:N-t-butyl-n'-tetradecyl-3-tetradecylaminopropionamidine; C476286:Ticam1 protein, mouse