title: Synthetic mycoplasma-derived lipopeptide MALP-2 induces maturation and function of dendritic cells.
abstract: Dendritic cells (DC) modulate immune responses depending on the nature of the antigens. Receptors capable of discriminating these antigens on the basis of the pathogen-associated molecular patterns (PAMP) belong to the Toll-like receptor (TLR) family. The macrophage-activating lipopeptide 2 kDa (MALP-2), a synthetic lipopeptide derived from Mycoplasma fermentans, signals through TLR-2 and TLR-6. The aim of this study was to examine whether MALP-2 can modulate the functional properties of human monocyte-derived DC. The effects of this treatment were compared to those of the TLR-4 agonist lipopolysaccharide (LPS). To ensure clinical applicability, DC were generated under serum-free conditions. MALP-2 and LPS stimulation induced the expression of CD83 and increased the expressions of CD80, CD86, HLA-ABC and CD40. Furthermore, both substances decreased the endocytotic capacity of DC and induced the release of bioactive TNF-alpha and IL-10, whereas LPS additionally increased IL-12 release. Pretreatment with both substances boosted the allostimulatory capacity of DC. In a coculture with autologous lymphocytes, either MALP-2 or LPS pretreated DC induced a marked proliferation of lymphocytes, but only DC prestimulated with MALP-2 activated lymphocytes to produce the cytokines IL-4, IL-5 and IFN-gamma. No polarisation of lymphocytes into T-helper (Th)1 or Th2 was detected. These data indicate that MALP-2 is a potential candidate to modulate DC for clinical applications.
authors.affiliation: Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany. weigt@item.fraunhofer.de
authors.forename: Henning
authors.initials: H
authors.lastname: Weigt
authors.forename: Peter F
authors.initials: PF
authors.lastname: Mühlradt
authors.forename: Andreas
authors.initials: A
authors.lastname: Emmendörffer
authors.forename: Norbert
authors.initials: N
authors.lastname: Krug
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000096:biosynthesis; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects*; D004705:Endocytosis; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D009174:Mycoplasma / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018417:Th1 Cells; D018418:Th2 Cells; D013997:Time Factors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D007136:Immunoglobulins; D007371:Interferon-gamma; D015847:Interleukin-4; D015848:Interleukin-5; D055666:Lipopeptides; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; D000097802:CD83 Antigen; C497964:CD86 protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; C106335:macrophage stimulatory lipopeptide 2