Modulation of immunoproteasome subunits by liposomal lipid A.
Liposomes are phospholipid vesicles that have been used as carriers of antigens and adjuvants. Lipid A, the endotoxic moiety of Gram-negative bacterial lipopolysaccharide is a potent adjuvant and incorporation into liposomes essentially reduces the endotoxic activity of lipid A. In this study, we analyzed the effect of liposomal lipid A [L(LA)] on the MHC class I antigen processing machinery in murine antigen presenting cells (APCs). L(LA) enhanced the surface expression of MHC class I, class II, CD80, and CD86 molecules, induced the secretion of IFN-gamma, IL-12p40, TNF-alpha and IL-10, and caused a shift in the proteasome profile from constitutive to immunoproteasomes as observed by the induction of beta2i, beta5i, PA28alpha, and PA28beta subunits. L(LA) acts through the production of IFN-gamma as demonstrated with APCs generated from IFN-gamma knockout mice. L(LA) therefore appears to act as an intracellular adjuvant by upregulating the antigen processing machinery, which could result in efficient antigen presentation.
Steers
Nicholas J
NJ
Division of Retrovirology, US Military HIV Research Program, Walter Reed Army Institute of Research, 1600 Gude Drive, Rockville, MD 20850, USA.
Alving
Carl R
CR
Rao
Mangala
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008050:Lipid A / Q000276:immunology*; D008081:Liposomes / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D016207:Cytokines; D004337:Drug Carriers; D008050:Lipid A; D008081:Liposomes; D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex