Related Experiment Video
Updated: Jul 6, 2026
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
DiC14-amidine cationic liposomes stimulate myeloid dendritic cells through Toll-like receptor 4
Tetsuya Tanaka1, Amandine Legat, Emmanuelle Adam
1Laboratoire d'Allergologie Expérimentale, Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires, Charleroi, Belgium.
Insights
DiC14-amidine cationic liposomes effectively stimulate dendritic cells (DC), promoting immune responses. This adjuvant utilizes Toll-like receptor 4 (TLR4) for MyD88 and TRIF-dependent signaling.
Area of Science:
- Immunology
- Cell Biology
- Vaccine Adjuvants
Background:
- Cationic liposomes, including DiC14-amidine, are investigated as vaccine adjuvants.
- DiC14-amidine has shown potential in promoting Th1 immune responses.
Purpose of the Study:
- To investigate the mechanism of action of DiC14-amidine as a vaccine adjuvant.
- To characterize the effects of DiC14-amidine on mouse and human myeloid dendritic cells (DC).
Main Methods:
- Comparing DiC14-amidine liposomes with other cationic liposomes.
- Assessing cytokine production (IL-12p40, TNF-alpha, IL-6, IFN-beta) and mRNA expression (CXCL10) in mouse and human DC.
- Analyzing cell surface marker expression (CD80, CD86) and intracellular signaling pathways (NF-kappaB, MAP kinases).
- Investigating the role of Toll-like receptor 4 (TLR4) and downstream signaling pathways (MyD88, TRIF).
Main Results:
- DiC14-amidine liposomes uniquely induced IL-12p40 and TNF-alpha in mouse DC compared to other liposomes.
- Human DC treated with DiC14-amidine showed increased IL-12p40, TNF-alpha, IL-6, IFN-beta, CXCL10 mRNA, and CD80/CD86 expression.
- DC activation involved NF-kappaB, ERK1/2, JNK, and p38 MAP kinase pathways.
- DiC14-amidine liposomes activate TLR4, leading to both MyD88-dependent and TRIF-dependent responses.
Conclusions:
- DiC14-amidine is a potent activator of both mouse and human myeloid dendritic cells.
- The adjuvant activity of DiC14-amidine is mediated through TLR4 signaling via MyD88 and TRIF pathways.
- DiC14-amidine represents a promising candidate for vaccine adjuvant development.
Abstract:
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.
