title: Enhancement of muramyldipeptide (MDP) immunostimulatory activity by controlled multimerization on dendrimers.
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.
authors: Innate Immunology Group, National Veterinary Institute, Technical University of Denmark, Copenhagen V, Denmark. nsor@vet.dtu.dk
authors: Nanna S
authors: NS
authors: Sorensen
authors: Ulrik
authors: U
authors: Boas
authors: Peter M H
authors: PM
authors: Heegaard
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000138:chemical synthesis* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D060887:B7 Antigens / Q000032:analysis / Q000096:biosynthesis; D050091:Dendrimers / Q000138:chemical synthesis* / Q000494:pharmacology; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000276:immunology; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D058105:Polymerization; D051192:Receptors, Pattern Recognition / Q000276:immunology / Q000378:metabolism; D013552:Swine
chemical_list: D000276:Adjuvants, Immunologic; D060887:B7 Antigens; D050091:Dendrimers; D053583:Interleukin-1beta; D015850:Interleukin-6; D051192:Receptors, Pattern Recognition; D018664:Interleukin-12; D000119:Acetylmuramyl-Alanyl-Isoglutamine