Mechanisms of Enhanced Antigen Delivery to Murine Dendritic Cells by the Cationic Liposomes

Abstract

There is an increased demand for vaccines to prevent and/or treat illness and mortality caused by the infectious diseases. We have recently established that liposomes composed of cationic lipids act as adjuvant for nasal vaccine formulation. However, the molecular mechanism(s) behind the adjuvant effect remain unrevealed. To this end, we have studied the enhancement of antigen uptake by murine dendritic cell line, DC2.4 cells, by the cationic liposomes and the specific pathways involved in the process. We have observed that the uptake of ovalbumin (OVA) into DC2.4 cells is greatly increased when co-cultured with the cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] (DC-chol). However, this enhancement was blocked by pretreatment of DC2.4 cells with chlorpromazine and methyl-β-cyclodextrin, indicating the involvement of clathrin- and caveolin-independent lipid raft-dependent endocytic pathways in the process. Our results implied, at least in part, that enhanced uptake of antigens induced by the cationic liposomes could be a possible mechanism for the induction of immune responses. Although further studies are needed to understand the precise mechanisms behind the adjuvant effects of DOTAP/DC-chol liposome, this approach is quite useful for the development of vaccine system to combat various diseases