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The Toll-like receptor ligand MALP-2 stimulates dendritic cell maturation and modulates proteasome composition and activity.
- Source :
-
European journal of immunology [Eur J Immunol] 2004 Mar; Vol. 34 (3), pp. 899-907. - Publication Year :
- 2004
-
Abstract
- A 2-kDa synthetic derivative of the macrophage-activating lipopeptide (MALP-2) from Mycoplasma fermentans is a potent inducer of monocytes/macrophages and improves the immunogenicity of antigens co-administered by systemic and mucosal routes. Dendritic cells (DC) are the most potent antigen-presenting cells, which are able to prime naive T cells in vivo. To elucidate the underlying mechanisms of MALP-2 adjuvanticity, we analyzed its activity on bone marrow-derived murine DC. In vitro stimulation of immature murine DC with MALP-2 resulted in the induction of maturation with up-regulated expression of MHC class II, costimulatory (CD80, CD86) and adhesion (CD40, CD54) molecules. MALP-2 also enhances the secretion of cytokines (IL-1alpha, IL-6 and IL-12), and increases DC stimulatory activity on naive and antigen-specific T cells. Further studies demonstrated that MALP-2 treatment of DC results in a dose-dependent shift from the protein pattern of proteasomes to immunoproteasomes (up-regulation of LMP2, LMP7 and MECL1), which correlates with an increased proteolytic activity. Thus, the adjuvanticity of MALP-2 can be mediated, at least in part, by the stimulation of DC maturation, which in turn leads to an improved antigen presentation. Therefore, MALP-2 is a promising molecule for the development of immune therapeutic or prophylactic interventions.
- Subjects :
- Animals
Antigen Presentation
Antigens, CD metabolism
Cell Adhesion Molecules metabolism
Cell Differentiation
Cysteine Endopeptidases chemistry
Cytokines biosynthesis
Dendritic Cells enzymology
Dendritic Cells immunology
Female
Histocompatibility Antigens Class II metabolism
Ligands
Lipopeptides
Lymphocyte Activation
Lymphocyte Culture Test, Mixed
Membrane Glycoproteins metabolism
Mice
Mice, Inbred BALB C
Multienzyme Complexes chemistry
Proteasome Endopeptidase Complex
Receptors, Cell Surface metabolism
T-Lymphocytes immunology
Toll-Like Receptors
Up-Regulation
Adjuvants, Immunologic pharmacology
Cysteine Endopeptidases metabolism
Dendritic Cells drug effects
Membrane Glycoproteins agonists
Multienzyme Complexes metabolism
Oligopeptides pharmacology
Receptors, Cell Surface agonists
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2980
- Volume :
- 34
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 14991620
- Full Text :
- https://doi.org/10.1002/eji.200324511