Abstract
Peptidoglycan is a widespread bacterial PAMP molecule and a powerful initiator of innate immune responses. It consists of repeating units of MDP, which as a monomer is only weakly immunostimulatory. Here, MDP-coupled dendrimers were prepared and investigated for stimulation of pig blood mononuclear cells. Compared to monomeric MDP, MDP-dendrimers induced a markedly enhanced production of IL-12 p40, IL-1β and IL-6 and completely down-regulated surface expression of B7 and MHC class II. These results suggest a possible novel strategy based on controlled multimerization of minimal PAMP motifs on dendrimers for preparing molecularly defined immunostimulators with predictable bioactivities.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylmuramyl-Alanyl-Isoglutamine / chemical synthesis*
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Acetylmuramyl-Alanyl-Isoglutamine / pharmacology
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Adjuvants, Immunologic / chemical synthesis*
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Adjuvants, Immunologic / pharmacology
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Animals
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B7 Antigens / analysis
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B7 Antigens / biosynthesis
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Dendrimers / chemical synthesis*
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Dendrimers / pharmacology
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Flow Cytometry
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Genes, MHC Class II / immunology
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Immunity, Innate*
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Interleukin-12 / biosynthesis
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Interleukin-1beta / biosynthesis
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Interleukin-6 / biosynthesis
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / drug effects*
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Lymphocyte Activation / drug effects*
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Lymphocyte Activation / immunology
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Polymerization
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Receptors, Pattern Recognition / immunology
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Receptors, Pattern Recognition / metabolism
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Swine
Substances
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Adjuvants, Immunologic
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B7 Antigens
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Dendrimers
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Interleukin-1beta
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Interleukin-6
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Receptors, Pattern Recognition
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Interleukin-12
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Acetylmuramyl-Alanyl-Isoglutamine